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Cao Z, Wang Z, Yang L, Li T, Tao X, Niu X. Reshaping the immune microenvironment and reversing immunosenescence by natural products: Prospects for immunotherapy in gastric cancer. Semin Cancer Biol 2025; 110:1-16. [PMID: 39923925 DOI: 10.1016/j.semcancer.2025.02.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/25/2025] [Accepted: 02/03/2025] [Indexed: 02/11/2025]
Abstract
Gastric cancer (GC) represents a global health-care challenge. Recent progress in immunotherapy has elicited attracted considerable attention as a viable treatment option through modulating the host immune system and unleashing pre-existing immunity, which has profoundly revolutionized oncology, especially GC. Nonetheless, low clinical response and intrinsic and acquired resistance remain persistently challenging. The microenvironment of GC comprising multifarious stromal cell types has remarkable immunosuppressive elements that may impact the efficacy of immunotherapy. Immunosenescence is increasingly regarded as a factor that contributes to cancer development, remodels the tumor microenvironment and affects the efficacy of immunotherapy. Natural products are at the forefront of traditional medicine. Senotherapeutics is a class of drugs and natural products capable of delaying, preventing, or reversing the senescence process (i.e., senolytics) or suppressing senescence-associated secretory phenotype (i.e., senomorphics). Emerging evidence supports that natural products can improve the efficacy of existing immunotherapy and expand their indications in GC mainly based upon remodeling the immunosuppressive microenvironment and reversing immunosenescence. The review provides an integrated review of previously reported and ongoing clinical trials with immunotherapeutic regimens in GC and discusses current challenges. Next, we focus on natural compounds that exert anti-GC functions and possess immunomodulatory properties. More attention is paid to the potential of these natural compounds in modulating the immune microenvironment and immunosenescence. Lastly, we discuss the nanomedicine that can overcome the deficiencies of natural products. Altogether, our review suggests the enormous potential of natural compounds in GC immunotherapy, and provides an important direction for future research.
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Affiliation(s)
- Zhipeng Cao
- Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, China
| | - Zhilin Wang
- Department of Pain Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Li Yang
- Department of Anesthesiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China
| | - Tian Li
- Tianjin Key Laboratory of Acute Abdomen Disease-Associated Organ Injury and ITCWM Repair, Institute of Integrative Medicine of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China.
| | - Xueshu Tao
- Department of Pain Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
| | - Xing Niu
- Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, China.
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Yuan H, Bao M, Chen M, Fu J, Yu S. Advances in Immunotherapy and Targeted Therapy for Gastric Cancer: A Comprehensive Review. Br J Hosp Med (Lond) 2025; 86:1-24. [PMID: 40135294 DOI: 10.12968/hmed.2024.0759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2025]
Abstract
Gastric cancer remains one of the most prevalent and lethal malignancies worldwide, characterized by poor survival rates, particularly in advanced stages. In recent years, a paradigm shift in gastric cancer treatment has been witnessed with the introduction of immunotherapy and targeted therapies. This review provides a detailed examination of current immunotherapeutic strategies, including adoptive cell therapy (ACT), immune checkpoint inhibitors (ICIs), and cancer vaccines. Additionally, it explores advancements in targeted therapies, focusing on the human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor receptor (VEGFR) signaling pathways, as well as emerging targets such as claudin 18.2. Clinical trials investigating chimeric antigen receptor T-cell (CAR-T) therapy, T-cell receptor-engineered T-cell (TCR-T) therapy, and natural killer (NK) cell-based treatments have shown promise, particularly when combined with conventional chemotherapeutic regimens. However, challenges such as cytokine release syndrome, immune-related toxicities, and scalability issues remain significant. The combination of immunotherapy with targeted therapies represents a promising approach to enhance treatment outcomes. Future directions emphasize the need to overcome resistance mechanisms and refine treatment strategies to improve efficacy while reducing adverse effects. This review aims to elucidate the current landscape of immunotherapy and targeted therapy in gastric cancer and to explore their potential in shaping the future of clinical management for this devastating disease.
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Affiliation(s)
- Hui Yuan
- Department of Hepatobiliary and Pancreatic Surgery, Jinhua Municipal Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China
| | - Miao Bao
- The Second Ward, Department of Pediatrics, Jinhua Maternal & Child Health Hospital, Jinhua, Zhejiang, China
| | - Minqiang Chen
- Department of Hepatobiliary and Pancreatic Surgery, Jinhua Municipal Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China
| | - Junhao Fu
- Central Laboratory, Jinhua Municipal Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China
| | - Shian Yu
- Department of Hepatobiliary and Pancreatic Surgery, Jinhua Municipal Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China
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Luo D, Liu Y, Lu Z, Huang L. Targeted therapy and immunotherapy for gastric cancer: rational strategies, novel advancements, challenges, and future perspectives. Mol Med 2025; 31:52. [PMID: 39923010 PMCID: PMC11806620 DOI: 10.1186/s10020-025-01075-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 01/10/2025] [Indexed: 02/10/2025] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors worldwide, and its treatment has been a focus of medical research. Herein we systematically review the current status of and advancements in targeted therapy and immunotherapy for GC, which have emerged as important treatment strategies in recent years with great potential, and summarize the efficacy and safety of such treatments. Targeted therapies against key targets in GC, including epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR), have shown remarkable therapeutic efficacies by inhibiting tumor progression and/or blood supply. In particular, markable breakthroughs have been made in HER2-targeting drugs for HER2-positive GC patients. To address intrinsic and acquired resistances to HER2-targeting drugs, novel therapeutic agents including bispecific antibodies and antibody-drug conjugates (ADC) targeting HER2 have been developed. Immunotherapy enhances the recognition and elimination of cancer cells by activating body anticancer immune system. Programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) antibodies are the most commonly used immunotherapeutic agents and have been used with some success in GC treatment. Innovative immunotherapy modalities, including adoptive immune cell therapy, tumor vaccines, and non-specific immunomodulators therapy, and oncolytic viruses have shown promise in early-stage clinical trials for GC. Clinical trials have supported that targeted therapy and immunotherapy can significantly improve the survival and quality of life of GC patients. However, the effects of such therapies need to be further improved and more personalized, with advancement in researches on tumor immune microenvironment. Further studies remain needed to address the issues of drug resistance and adverse events pertaining to such therapies for GC. The combined application of such therapies and individualized treatment strategies should be further explored with novel drugs developed, to provide more effective treatments for GC patients.
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Affiliation(s)
- Dong Luo
- Department of Gastroenterology, National Clinical Research Center for Digestive Diseases, The First Affiliated Hospital of Naval Medical University/Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
- Center of Structural Heart Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yunmei Liu
- School of Cultural Heritage and Information Management, Shanghai University, Shanghai, 200444, China.
| | - Zhengmao Lu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
| | - Lei Huang
- Department of Gastroenterology, National Clinical Research Center for Digestive Diseases, The First Affiliated Hospital of Naval Medical University/Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.
- National Key Laboratory of Immunity and Inflammation, Changhai Clinical Research Unit, The First Affiliated Hospital of Naval Medical University/Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.
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SANTOS MARTA, MARTINS DIANA, MENDES FERNANDO. Immunotherapy in gastric cancer-A systematic review. Oncol Res 2025; 33:263-281. [PMID: 39866237 PMCID: PMC11753986 DOI: 10.32604/or.2024.052207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 11/22/2024] [Indexed: 01/28/2025] Open
Abstract
Background Gastric Cancer (GC) is the 5th most prevalent and 4th most deadly neoplasm globally. Immunotherapy has emerged as a promising treatment approach in GC, potentially improving positive clinical outcomes while addressing the limitations of conventional therapies. GC immunotherapy modalities consist of adoptive cell therapy (ACT), cancer vaccines, and immune checkpoint inhibitors (ICI). Objectives This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC, highlighting the potential of this therapy as a strategy for GC treatment. Methods Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study. Specific cancer outcomes related to disease progression or survival were analyzed. Results After screening 236 studies, the results revealed that immunotherapy, particularly the ICI pembrolizumab, demonstrated promising efficacy in the treatment of GC, as several studies reported improved OS, PFS, and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities. Conclusion Safety analysis showed that immunotherapy was mostly well-tolerated, with manageable adverse events and relatively good safety profiles. Nonetheless, further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.
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Affiliation(s)
- MARTA SANTOS
- Polytechnic University of Coimbra, ESTESC, UCPCBL, Rua 5 de Outubro, SM Bispo, Apartado, Coimbra, 3046-854, Portugal
| | - DIANA MARTINS
- Polytechnic University of Coimbra, ESTESC, UCPCBL, Rua 5 de Outubro, SM Bispo, Apartado, Coimbra, 3046-854, Portugal
- H&TRC–Health & Technology Research Center, Coimbra Health School, Polytechnic University of Coimbra, Coimbra, 3046-854, Portugal
- Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Biophysics Institute of Faculty of Medicine, University of Coimbra, Coimbra, 3000-548, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, 3000-548, Portugal
| | - FERNANDO MENDES
- Polytechnic University of Coimbra, ESTESC, UCPCBL, Rua 5 de Outubro, SM Bispo, Apartado, Coimbra, 3046-854, Portugal
- H&TRC–Health & Technology Research Center, Coimbra Health School, Polytechnic University of Coimbra, Coimbra, 3046-854, Portugal
- Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Biophysics Institute of Faculty of Medicine, University of Coimbra, Coimbra, 3000-548, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, 3000-548, Portugal
- European Association of Biomedical Scientists, Brussels, 1000, Belgium
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Yang M, Lin W, Huang J, Mannucci A, Luo H. Novel immunotherapeutic approaches in gastric cancer. PRECISION CLINICAL MEDICINE 2024; 7:pbae020. [PMID: 39397869 PMCID: PMC11467695 DOI: 10.1093/pcmedi/pbae020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 09/08/2024] [Accepted: 09/08/2024] [Indexed: 10/15/2024] Open
Abstract
Gastric cancer is a malignant tumor that ranks third in cancer-related deaths worldwide. Early-stage gastric cancer can often be effectively managed through surgical resection. However, the majority of cases are diagnosed in advanced stages, where outcomes with conventional radiotherapy and chemotherapy remain unsatisfactory. Immunotherapy offers a novel approach to treating molecularly heterogeneous gastric cancer by modifying the immunosuppressive tumor microenvironment. Immune checkpoint inhibitors and adoptive cell therapy are regarded as promising modalities in cancer immunotherapy. Food and Drug Administration-approved programmed death-receptor inhibitors, such as pembrolizumab, in combination with chemotherapy, have significantly extended overall survival in gastric cancer patients and is recommended as a first-line treatment. Despite challenges in solid tumor applications, adoptive cell therapy has demonstrated efficacy against various targets in gastric cancer treatment. Among these approaches, chimeric antigen receptor-T cell therapy research is the most widely explored and chimeric antigen receptor-T cell therapy targeting claudin18.2 has shown acceptable safety and robust anti-tumor capabilities. However, these advancements primarily remain in preclinical stages and further investigation should be made to promote their clinical application. This review summarizes the latest research on immune checkpoint inhibitors and adoptive cell therapy and their limitations, as well as the role of nanoparticles in enhancing immunotherapy.
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Affiliation(s)
- Meng Yang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China
| | - Wuhao Lin
- Department of Molecular Diagnostics, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Jiaqian Huang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China
| | - Alessandro Mannucci
- Gastroenterology and Gastrointestinal Emndoscopy Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan 20132, Italy
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope; Monrovia, CA 91016, USA
| | - Huiyan Luo
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China
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Nakayama I, Shitara K. The current status of immunotherapy and future horizon in the treatment of metastatic and locally advanced gastroesophageal adenocarcinoma. Expert Opin Biol Ther 2024; 24:903-915. [PMID: 39171531 DOI: 10.1080/14712598.2024.2395921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 07/23/2024] [Accepted: 08/20/2024] [Indexed: 08/23/2024]
Abstract
INTRODUCTION Immunochemotherapy with PD-1 blockade has been established as the current standard first-line therapy for patients with mGEA. Reviewing the history of clinical trials offers valuable insight into the evolution of immune oncology in mGEA, paving the way for future advancements in this field. AREAS COVERED This review summarizes the findings of previous clinical trials related to immunotherapy for patients with GEA in the metastatic and locally advanced setting. We also introduce ongoing clinical trials to address the current challenging issues in clinical practice. EXPERT OPINION In general, GEA exhibits intermediate immunogenic characteristics with heterogeneous expressions, and responders to anti-PD-(L)1 therapy are mostly enriched to patients with specific genomic profiles such as MSI-H, high PD-L1 expression, high TMB, and EBV-associated type. Co-administration with anti-angiogenic agents or simultaneous blockade of immune checkpoint molecules is being explored to offer benefit of immunotherapy for more patients. We hope that CLDN18.2 and upcoming targets like FGFR2b will complement the treatment niche of immunotherapy in the field of mGEA. Bispecific antibodies, antibody drug conjugates, CAR-T, and vaccine are anticipated to enhance efficacy and expand the scope of immunotherapy.
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Affiliation(s)
- Izuma Nakayama
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Kohei Shitara
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
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Poniewierska-Baran A, Sobolak K, Niedźwiedzka-Rystwej P, Plewa P, Pawlik A. Immunotherapy Based on Immune Checkpoint Molecules and Immune Checkpoint Inhibitors in Gastric Cancer-Narrative Review. Int J Mol Sci 2024; 25:6471. [PMID: 38928174 PMCID: PMC11203505 DOI: 10.3390/ijms25126471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/31/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
Due to its rapid progression to advanced stages and highly metastatic properties, gastric cancer (GC) is one of the most aggressive malignancies and the fourth leading cause of cancer-related deaths worldwide. The metastatic process includes local invasion, metastasis initiation, migration with colonisation at distant sites, and evasion of the immune response. Tumour growth involves the activation of inhibitory signals associated with the immune response, also known as immune checkpoints, including PD-1/PD-L1 (programmed death 1/programmed death ligand 1), CTLA-4 (cytotoxic T cell antigen 4), TIGIT (T cell immunoreceptor with Ig and ITIM domains), and others. Immune checkpoint molecules (ICPMs) are proteins that modulate the innate and adaptive immune responses. While their expression is prominent on immune cells, mainly antigen-presenting cells (APC) and other types of cells, they are also expressed on tumour cells. The engagement of the receptor by the ligand is crucial for inhibiting or stimulating the immune cell, which is an extremely important aspect of cancer immunotherapy. This narrative review explores immunotherapy, focusing on ICPMs and immune checkpoint inhibitors in GC. We also summarise the current clinical trials that are evaluating ICPMs as a target for GC treatment.
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Affiliation(s)
- Agata Poniewierska-Baran
- Center of Experimental Immunology and Immunobiology of Infectious and Cancer Diseases, University of Szczecin, 71-417 Szczecin, Poland; (A.P.-B.); (P.N.-R.)
- Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland
| | - Karolina Sobolak
- Students Research Club of Immunobiology of Infectious and Cancer Diseases “NEUTROPHIL”, University of Szczecin, 71-417 Szczecin, Poland; (K.S.); (P.P.)
| | - Paulina Niedźwiedzka-Rystwej
- Center of Experimental Immunology and Immunobiology of Infectious and Cancer Diseases, University of Szczecin, 71-417 Szczecin, Poland; (A.P.-B.); (P.N.-R.)
- Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland
| | - Paulina Plewa
- Students Research Club of Immunobiology of Infectious and Cancer Diseases “NEUTROPHIL”, University of Szczecin, 71-417 Szczecin, Poland; (K.S.); (P.P.)
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland
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Yao J, Tan X, Sha Y, Chen Y, Chen R, Shi D. An updated review of immunotherapy in esophageal cancer: PD-L1 footprint. Cent Eur J Immunol 2024; 49:77-90. [PMID: 38812606 PMCID: PMC11130989 DOI: 10.5114/ceji.2024.139269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 12/15/2023] [Indexed: 05/31/2024] Open
Abstract
Esophageal cancer is considered one of the most significant challenges to public health worldwide. While various therapeutic options exist for esophageal cancer, including chemotherapy, radiotherapy, and surgery, several adverse effects of these medications have been reported. Therefore, a new generation of therapeutic lines should be applied to minimize complications. In this regard, immunotherapy is a novel approach that aims to kill tumor cells directly by targeting them. Specifically, monoclonal antibodies can target specific markers of esophageal cancer tumor cells, keeping other normal cells safe. Multiple monoclonal antibodies optimized for esophageal cancer, such as pembrolizumab, ramucirumab, trastuzumab, nivolumab, and ipilimumab, are available. On the other hand, esophageal cancer tumor cells express a specific inhibitory ligand and its receptor called programmed cell death, which can suppress T cell immune responses. This receptor provides an inhibitory signal, causing the highest expression of the PD-L1 ligand on tumor cells. The outcomes of this interaction lead to the suppression of the activation and function of T lymphocytes. Therefore, immunotherapy for esophageal cancer targeting the PD-1/PD-L1 pathway has shown a remarkable correlation with cancer care. This study presents a comprehensive review of the latest findings related to immunotherapy in esophageal cancer.
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Affiliation(s)
- Juan Yao
- Department of Radiation Oncology, Huaian Hospital of Huaian City (Huai’a Cancer Hospital), Huaian, Jiangsu 223200, P.R. of China
| | - Xiaoyan Tan
- Department of Obstetrics and Gynecology, Huaian Hospital of Huaian City (Huai’an Cancer Hospital), Huaian, Jiangsu 223200, P.R. of China
| | - Yanping Sha
- Department of Radiation Oncology, Huaian Hospital of Huaian City (Huai’a Cancer Hospital), Huaian, Jiangsu 223200, P.R. of China
| | - Yurao Chen
- Department of Radiation Oncology, Huaian Hospital of Huaian City (Huai’a Cancer Hospital), Huaian, Jiangsu 223200, P.R. of China
| | - Ronghuai Chen
- Department of Radiation Oncology, Huaian Hospital of Huaian City (Huai’a Cancer Hospital), Huaian, Jiangsu 223200, P.R. of China
| | - Dongping Shi
- Department of Infection, Huaian Hospital of Huaian City (Huai’a Cancer Hospital), Huaian, Jiangsu 223200, P.R. of China
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Shebbo S, Binothman N, Darwaish M, Niaz HA, Abdulal RH, Borjac J, Hashem AM, Mahmoud AB. Redefining the battle against colorectal cancer: a comprehensive review of emerging immunotherapies and their clinical efficacy. Front Immunol 2024; 15:1350208. [PMID: 38533510 PMCID: PMC10963412 DOI: 10.3389/fimmu.2024.1350208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 02/21/2024] [Indexed: 03/28/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer globally and presents a significant challenge owing to its high mortality rate and the limitations of traditional treatment options such as surgery, radiotherapy, and chemotherapy. While these treatments are foundational, they are often poorly effective owing to tumor resistance. Immunotherapy is a groundbreaking alternative that has recently emerged and offers new hope for success by exploiting the body's own immune system. This article aims to provide an extensive review of clinical trials evaluating the efficacy of various immunotherapies, including CRC vaccines, chimeric antigen receptor T-cell therapies, and immune checkpoint inhibitors. We also discuss combining CRC vaccines with monoclonal antibodies, delve into preclinical studies of novel cancer vaccines, and assess the impact of these treatment methods on patient outcomes. This review seeks to provide a deeper understanding of the current state of CRC treatment by evaluating innovative treatments and their potential to redefine the prognosis of patients with CRC.
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Affiliation(s)
- Salima Shebbo
- Strategic Research and Innovation Laboratories, Taibah University, Madinah, Saudi Arabia
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Biological Sciences, Beirut Arab University, Debbieh, Lebanon
| | - Najat Binothman
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Chemistry, College of Sciences and Arts, King Abdulaziz University, Rabigh, Saudi Arabia
| | - Manar Darwaish
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Immunology Research Program, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Hanan A. Niaz
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Rwaa H. Abdulal
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Jamilah Borjac
- Department of Biological Sciences, Beirut Arab University, Debbieh, Lebanon
| | - Anwar M. Hashem
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ahmad Bakur Mahmoud
- Strategic Research and Innovation Laboratories, Taibah University, Madinah, Saudi Arabia
- College of Applied Medical Sciences, Taibah University, Almadinah Almunawarah, Saudi Arabia
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Wang Y, Guo F, Song W, Guo W, Shao J, Liu Y. Crosstalk of cuproptosis-related subtypes, establishment of a prognostic signature, and immune infiltration characteristics in gastric cancer. Heliyon 2024; 10:e24411. [PMID: 38298669 PMCID: PMC10827783 DOI: 10.1016/j.heliyon.2024.e24411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Revised: 01/05/2024] [Accepted: 01/08/2024] [Indexed: 02/02/2024] Open
Abstract
Background Cuproptosis is a novel form of cellular demise that occurs through a unique pathway involving lipoylated proteins in the tricarboxylic acid (TCA) cycle and is closely linked to mitochondrial metabolism. Nevertheless, the comprehensive elucidation of the impact of carcinogenesis-associated genes (CRGs) on prognosis, tumor microenvironment (TME), and therapeutic response in patients with gastric cancer (GC) remains unclear. Methods In total, 1374 GC samples were gathered from three Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas database. The samples were then stratified into different subtypes through unsupervised clustering of the 13 CRG profiles. The CRG_score was developed to quantify CRG patterns of individual tumors. Subsequently, we investigated the associations among the various groups and clinicopathological features, immune infiltration features, TME mutation status, and response to immunotherapy. Results The GC samples were divided into two clusters based on their distinct clinicopathological features, prognosis, and immune characteristics. Using LASSO and Cox regression analyses, 9 genes were identified for constructing a prognostic signature related to cuproptosis. The novel signature displayed outstanding durability and prognostic capability for the overall lifespan of individuals. Additionally, the expression levels of signature genes in GC tissues and adjacent normal tissues were tested by qRT-PCR. Moreover, we developed a remarkably dependable nomogram to enhance the practicality of the CRG_score in clinical settings. High tumor mutation burden, increased microsatellite instability-high, immune activation, along with good survival probability and increased immunoreactivity to immune checkpoint inhibitors, were distinguishing features of low CRG_scores. Conclusions The findings of this study revealed the possible impacts of CRGs on the TME, clinical and pathological characteristics, and outlook of patients with GC. This signature was strongly linked to the immune response against GC and has the potential to serve as a valuable tool for predicting patient prognosis.
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Affiliation(s)
- Yatao Wang
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China
| | - Fengqin Guo
- Department of Obstetrics & Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China
| | - Wei Song
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China
| | - Wenyi Guo
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China
| | - Junwei Shao
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China
| | - Yanliang Liu
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China
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Yu X, Zhai X, Wu J, Feng Q, Hu C, Zhu L, Zhou Q. Evolving perspectives regarding the role of the PD-1/PD-L1 pathway in gastric cancer immunotherapy. Biochim Biophys Acta Mol Basis Dis 2024; 1870:166881. [PMID: 37696462 DOI: 10.1016/j.bbadis.2023.166881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 08/08/2023] [Accepted: 09/04/2023] [Indexed: 09/13/2023]
Abstract
Gastric cancer (GC) is an increasing global health problem and is one of the leading cancers worldwide. Traditional therapies, such as radiation and chemotherapy, have made limited progress in enhancing their efficacy for advanced GC. The development of immunotherapy for advanced GC has considerably improved with a deeper understanding of the tumor microenvironment. Immunotherapy using checkpoint inhibitors is a new therapeutic option that has made substantial advances in the treatment of other malignancies and is increasingly used in other clinical oncology treatments. Particularly, therapeutic antibodies targeting the programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have been effectively used in the clinical treatment of cancer. Monoclonal antibodies blocking the PD-1/PD-L1 pathway have been developed for cancer immunotherapy to enhance T cell function to restore the immune response and represent a breakthrough in the treatment of GC. This review provides an outline of the progress of PD-1/PD-L1 blockade therapy and its expression characteristics and clinical application in advanced GC.
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Affiliation(s)
- Xianzhe Yu
- Department of Medical Oncology, Cancer Center & Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China; Department of Gastrointestinal Surgery, Chengdu Second People's Hospital, No. 10 Qinyun Nan Street, Chengdu, Sichuan Province, People's Republic of China
| | - Xiaoqian Zhai
- Department of Medical Oncology, Cancer Center & Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Juan Wu
- Out-patient Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Qingbo Feng
- Department of General Surgery, Affiliated Hospital of Zunyi Medical University, Affiliated Digestive Hospital of Zunyi Medical University, Zunyi, Guizhou Province, People's Republic of China
| | - Chenggong Hu
- Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
| | - Lingling Zhu
- Department of Medical Oncology, Cancer Center & Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
| | - Qinghua Zhou
- Department of Medical Oncology, Cancer Center & Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
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Shaopeng Z, Yang Z, Yuan F, Chen H, Zhengjun Q. Regulation of regulatory T cells and tumor-associated macrophages in gastric cancer tumor microenvironment. Cancer Med 2024; 13:e6959. [PMID: 38349050 PMCID: PMC10839124 DOI: 10.1002/cam4.6959] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 01/10/2024] [Accepted: 01/14/2024] [Indexed: 02/15/2024] Open
Abstract
INTRODUCTION Despite advancements in the methods for prevention and early diagnosis of gastric cancer (GC), GC continues to be the fifth in incidence among major cancers and the third most common cause of cancer-related death. The therapeutic effects of surgery and drug treatment are still unsatisfied and show notable differences according to the tumor microenvironment (TME) of GC. METHODS Through screening Pubmed, Embase, and Web of Science, we identified and summarized the content of recent studies that focus on the investigation of Helicobacter pylori (Hp) infection, regulatory T cells (Tregs), and tumor-associated macrophages (TAMs) in the TME of GC. Furthermore, we searched and outlined the clinical research progress of various targeted drugs in GC treatment including CTLA-4, PD-1\PD-L1, and VEGF/VEGFR. RESULTS In this review, the findings indicate that Hp infection causes local inflammation and leads to immunosuppressive environment. High Tregs infiltration in the TME of GC is associated with increased induction and recruitment; the exact function of infiltrated Tregs in GC was also affected by phenotypes and immunosuppressive molecules. TAMs promote the development and metastasis of tumors, the induction, recruitment, and function of TAMs in the TME of gastric cancer are also regulated by various factors. CONCLUSION Discussing the distinct tumor immune microenvironment (TIME) of GC can deepen our understanding on the mechanism of cancer immune evasion, invasion, and metastasis, help us to reduce the incidence of GC, and guide the innovation of new therapeutic targets for GC eventually.
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Affiliation(s)
- Zhang Shaopeng
- Department of Gastrointestinal Surgery, Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Zheng Yang
- Department of Gastrointestinal Surgery, Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Fang Yuan
- Department of Gastrointestinal Surgery, Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Huang Chen
- Department of Gastrointestinal Surgery, Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Qiu Zhengjun
- Department of Gastrointestinal Surgery, Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghaiChina
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Sato Y, Yamashita H, Kobayashi Y, Nagaoka K, Hisayoshi T, Kawahara T, Kuroda A, Saito N, Iwata R, Okumura Y, Yagi K, Aiko S, Nomura S, Kakimi K, Seto Y. Alterations in Intratumoral Immune Response before and during Early-On Nivolumab Treatment for Unresectable Advanced or Recurrent Gastric Cancer. Int J Mol Sci 2023; 24:16602. [PMID: 38068925 PMCID: PMC10706573 DOI: 10.3390/ijms242316602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/16/2023] [Accepted: 11/19/2023] [Indexed: 12/18/2023] Open
Abstract
We investigated the tumor immune response in gastric cancer patients receiving third-line nivolumab monotherapy to identify immune-related biomarkers for better patient selection. Nineteen patients (10 males, median age 67 years) who received nivolumab as a third- or later-line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients. Pre-treatment and early-on-treatment tumor transcriptomes were examined, and gene expression profiles, immunograms, and T cell receptor (TCR) repertoire were analyzed. DCB was observed in 15.8% of patients, with comparable secondary endpoints (ORR; objective response rate, OS; overall survival, PFS; progression-free survival) to previous trials. The immunograms of individual subjects displayed no significant changes before or early in the treatment, except for the regulatory T cell (Treg) score. Moreover, there were no consistent alterations observed among cases experiencing DCB. The intratumoral immune response was suppressed by previous treatments in most third- or later-line nivolumab recipients. TCR repertoire analysis revealed newly emerged clonotypes in early-on-treatment tumors, but clonal replacement did not impact efficacy. High T cell/Treg ratios and a low UV-radiation-response gene signature were linked to DCB and treatment response. This study emphasizes the tumor immune response's importance in nivolumab efficacy for gastric cancer. High T cell/Treg ratios and specific gene expression signatures show promise as potential biomarkers for treatment response. The tumor-infiltrating immune response was compromised by prior treatments in third-line therapy, implying that, to enhance immunotherapeutic outcomes, commencing treatment at an earlier stage might be preferable. Larger cohort validation is crucial to optimize immune-checkpoint inhibitors in gastric cancer treatment.
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Affiliation(s)
- Yasuyoshi Sato
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
- Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.K.); (K.N.)
- Department of Chemotherapy and Cancer Center, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Hiroharu Yamashita
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
- Department of Digestive Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Yukari Kobayashi
- Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.K.); (K.N.)
| | - Koji Nagaoka
- Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.K.); (K.N.)
| | | | - Takuya Kawahara
- Clinical Research Promotion Center, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan;
| | - Akihiro Kuroda
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
- Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.K.); (K.N.)
| | - Noriyuki Saito
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
| | - Ryohei Iwata
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
- Department of Digestive Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Yasuhiro Okumura
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
| | - Koichi Yagi
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
| | - Susumu Aiko
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
| | - Sachiyo Nomura
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
| | - Kazuhiro Kakimi
- Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.K.); (K.N.)
- Department of Immunology, Kindai University Faculty of Medicine, Osakasayama-shi 589-8511, Japan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.S.); (H.Y.); (A.K.); (N.S.); (R.I.); (Y.O.); (K.Y.); (S.A.); (S.N.); (Y.S.)
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Cheng R, Li B, Wang H, Zeng Y. Immune checkpoint inhibitors and cellular immunotherapy for advanced gastric, gastroesophageal cancer: a long pathway. Clin Transl Oncol 2023; 25:3122-3138. [PMID: 37036597 DOI: 10.1007/s12094-023-03181-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 03/28/2023] [Indexed: 04/11/2023]
Abstract
Although the incidence rate and mortality of gastric/gastroesophageal cancer (G/GEJC) are declining globally, G/GEJC remains a health issue in East Asia. When diagnosed as advanced stage, treatment after serial lines of chemotherapy is limited, with a median overall survival of less than 1 year. Immunotherapy, including immune checkpoint inhibitors (ICIs) and cellular immunotherapy, has changed the prospects of cancer therapy by reversing immune suppression in the tumor microenvironment. As part of this review, we enumerated the clinical uses of ICIs related to the immunosuppressive signaling axis PD-1/PD-L1 and CTLA-4/B7. ICIs were initially approved as a secondary treatment option for patients with severe pretreating advanced gastric and gastroesophageal cancer (AG/GEJC). Till now, it has become the mainstream therapy in combination with chemotherapy and targeted therapy for patients identified by biomarkers. Numerous evidence showed microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and Epstein-Barr virus (EBV) status might be indicative to the use of ICIs. In addition, we discussed the current limitations and prospects of ICIs in AG/GGEJC, as well as the first clinical application of novel CAR-T cell therapies.
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Affiliation(s)
- Runzi Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China
- Shantou University Medical College, Shantou, People's Republic of China
| | - Baizhi Li
- Shantou University Medical College, Shantou, People's Republic of China
| | - Huaiming Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China
| | - Yongming Zeng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China.
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15
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Al-Batran SE, Mueller DW, Rafiyan MR, Kiselicki D, Atmaca A, Habibzada T, Mueller C, Brignone C, Triebel F, Loose M, Schaaf M, Sookthai D, Eickhoff R, Jaeger E, Goetze TO. A soluble LAG-3 protein (eftilagimod alpha) and an anti-PD-L1 antibody (avelumab) tested in a phase I trial: a new combination in immuno-oncology. ESMO Open 2023; 8:101623. [PMID: 37742484 PMCID: PMC10594027 DOI: 10.1016/j.esmoop.2023.101623] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 09/26/2023] Open
Abstract
BACKGROUND Eftilagimod alpha (efti) is a major histocompatibility complex class II agonist activating antigen-presenting cells which leads to greater systemic type 1 T helper response and more cytotoxic CD8+ T-cell activation. This phase I trial evaluated the administration of efti, a soluble lymphocyte activation gene-3 (LAG-3) protein, combined with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab in advanced solid tumors. PATIENTS AND METHODS Patients with heavily pretreated metastatic solid tumors received intravenous avelumab (800 mg) combined with subcutaneously administered efti (6 or 30 mg) for up to 12 cycles, followed by avelumab monotherapy. The primary endpoint was the assessment of the recommended phase II dose (RP2D) of efti in combination with avelumab. RESULTS Twelve patients with different tumor entities were enrolled (six patients in each cohort). During treatment, no dose-limiting toxicities occurred, and the severity of most adverse events was grade 1 or 2. In total, nine serious adverse events were documented, resulting in a fatal outcome in two cases, but none of them were assessed to be treatment related. Five patients (42%) achieved partial response. The median progression-free survival was 1.96 months and the median overall survival was not reached, with a 12-month survival rate of 75%. CONCLUSION Subcutaneously administered efti plus avelumab was well tolerated, and efti of 30 mg was determined to be RP2D. The activity is promising and warrants further investigation in future phase II trials.
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Affiliation(s)
- S-E Al-Batran
- UCT-University Cancer Center, Hospital Northwest, Frankfurt am Main; Institute of Clinical Cancer Research IKF at Hospital Northwest, Frankfurt am Main.
| | - D W Mueller
- Institute of Clinical Cancer Research IKF at Hospital Northwest, Frankfurt am Main
| | - M-R Rafiyan
- Department of Oncology and Hematology, Hospital Northwest, Frankfurt am Main
| | - D Kiselicki
- Department of Oncology and Hematology, Hospital Northwest, Frankfurt am Main
| | - A Atmaca
- Department of Oncology and Hematology, Hospital Northwest, Frankfurt am Main
| | - T Habibzada
- UCT-University Cancer Center, Hospital Northwest, Frankfurt am Main
| | | | | | | | - M Loose
- Institute of Clinical Cancer Research IKF at Hospital Northwest, Frankfurt am Main
| | - M Schaaf
- Institute of Clinical Cancer Research IKF at Hospital Northwest, Frankfurt am Main
| | - D Sookthai
- Institute of Clinical Cancer Research IKF at Hospital Northwest, Frankfurt am Main
| | - R Eickhoff
- Institute of Clinical Cancer Research IKF at Hospital Northwest, Frankfurt am Main
| | - E Jaeger
- Department of Oncology and Hematology, Hospital Northwest, Frankfurt am Main
| | - T O Goetze
- UCT-University Cancer Center, Hospital Northwest, Frankfurt am Main; Institute of Clinical Cancer Research IKF at Hospital Northwest, Frankfurt am Main
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Zheng L, Li M, Wei J, Chen S, Xue C, Duan Y, Tang F, Li G, Xiong W, She K, Deng H, Zhou M. NOP2/Sun RNA methyltransferase 2 is a potential pan-cancer prognostic biomarker and is related to immunity. PLoS One 2023; 18:e0292212. [PMID: 37769000 PMCID: PMC10538670 DOI: 10.1371/journal.pone.0292212] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 09/13/2023] [Indexed: 09/30/2023] Open
Abstract
BACKGROUND NOP2/Sun RNA methyltransferase 2 (NSUN2), an important methyltransferase of m5C, has been poorly studied in cancers, and the relationship between NSUN2 and immunity remains largely unclear. Therefore, the purpose of this study was to explore the expression and prognostic value of NSUN2 and the role of NSUN2 in immunity in cancers. METHODS The TIMER, CPTAC and other databases were used to analyze the expression of NSUN2, its correlation with clinical stage and its prognostic value across cancers. Moreover, the TISIDB, TIMER2.0 and Sangerbox platform were used to depict the relationships between NSUN2 and immune molecular subtypes, tumor-infiltrating lymphocytes (TILs), immune checkpoints (ICPs) and immunoregulatory genes. Furthermore, the NSUN2-interacting proteins and related genes as well as the coexpression networks of NSUN2 in LIHC, LUAD and HNSC were explored with the STRING, DAVID, GEPIA2 and LinkedOmics databases. Finally, the subcellular location and function of NSUN2 in HepG2, A549 and 5-8F cells were investigated by performing immunofluorescence, CCK-8 and wound healing assays. RESULTS Overall, NSUN2 was highly expressed and related to a poor prognosis in most types of cancers and was also significantly associated with immune molecular subtypes in some cancer types. Furthermore, NSUN2 was significantly associated with the levels of ICPs and immunoregulatory genes. In addition, NSUN2 was found to be involved in a series of immune-related biological processes, such as the humoral immune response in LIHC and LUAD and T-cell activation and B-cell activation in HNSC. Immunofluorescence and CCK-8 assays also confirmed that NSUN2 was widely expressed in the nucleus and cytoplasm, and overexpression of NSUN2 promoted the proliferation and migration of HepG2, A549 and 5-8F cells. NSUN2 was also confirmed to positively regulate the expression of PD-L1. CONCLUSION NSUN2 serves as a pan-cancer prognostic biomarker and is correlated with the immune infiltration of tumors.
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Affiliation(s)
- Lemei Zheng
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
| | - Mengna Li
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
| | - Jianxia Wei
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
| | - Shipeng Chen
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
| | - Changning Xue
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
| | - Yumei Duan
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
| | - Faqing Tang
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Guiyuan Li
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
| | - Kelin She
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- Department of Thoracic Surgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Hongyu Deng
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Ming Zhou
- NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
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Li M, Zhao Z, Mak TK, Wang X, Chen J, Ren H, Yu Z, Zhang C. Neutrophil extracellular traps-related signature predicts the prognosis and immune infiltration in gastric cancer. Front Med (Lausanne) 2023; 10:1174764. [PMID: 37636564 PMCID: PMC10447905 DOI: 10.3389/fmed.2023.1174764] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 07/27/2023] [Indexed: 08/29/2023] Open
Abstract
Introduction Gastric cancer (GC) is the fifth most prevalent cancer globally, with the third highest case fatality rate. Neutrophil extracellular traps (NETs) are a reticulated structure of DNA, histones, and antimicrobial peptides produced by active neutrophils that trap pathogens. Even though NETs are associated with poorer recurrence-free survival (RFS) and overall survival (OS), the specifics of this interaction between NETs and cancer cells are yet unknown. Methods The keywords "neutrophil extracellular traps and gastric cancer" were used in the GEO database for retrieval, and the GSE188741 dataset was selected to obtain the NETs-related gene. 27 NETs-related genes were screened by univariate Cox regression analysis (p < 0.05). 27 NETs-related genes were employed to identify and categorize NETs-subgroups of GC patients under the Consensus clustering analysis. 808 GC patients in TCGA-STAD combined with GES84437 were randomly divided into a training group (n = 403) and a test group (n = 403) at a ratio of 1:1 to validate the NETs-related signature. Results Based on Multivariate Cox regression and LASSO regression analysis to develop a NETs-related prognosis model. We developed a very specific nomogram to improve the NETs-clinical score's usefulness. Similarly, we also performed a great result in pan-cancer study with NETs-score. Low NETs scores were linked to higher MSI-H (microsatellite instability-high), mutation load, and immune activity. The cancer stem cell (CSC) index and chemotherapeutic treatment sensitivity were also connected to the NET score. Our comprehensive analysis of NETs in GC suggests that NETs have a role in the tumor microenvironment, clinicopathological features, and prognosis. Discussion The NETs-score risk model provides a basis for better prognosis and therapy outcomes in GC patients.
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Affiliation(s)
- Mingzhe Li
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Zidan Zhao
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Tsz Kin Mak
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Xiaoqun Wang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Jingyao Chen
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Hui Ren
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Zhiwei Yu
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Changhua Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
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Liu Y, Hu P, Xu L, Zhang X, Li Z, Li Y, Qiu H. Current Progress on Predictive Biomarkers for Response to Immune Checkpoint Inhibitors in Gastric Cancer: How to Maximize the Immunotherapeutic Benefit? Cancers (Basel) 2023; 15:2273. [PMID: 37190201 PMCID: PMC10137150 DOI: 10.3390/cancers15082273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/09/2023] [Accepted: 04/10/2023] [Indexed: 05/17/2023] Open
Abstract
Gastric cancer is the fifth most prevalent cancer and the fourth leading cause of cancer death globally. Delayed diagnosis and pronounced histological and molecular variations increase the complexity and challenge of treatment. Pharmacotherapy, which for a long time was systemic chemotherapy based on 5-fluorouracil, is the mainstay of management for advanced gastric cancer. Trastuzumab and programmed cell death 1 (PD-1) inhibitors have altered the therapeutic landscape, contributing to noticeably prolonged survivorship in patients with metastatic gastric cancer. However, research has revealed that immunotherapy is only beneficial to some individuals. Biomarkers, such as programmed cell death ligand 1 (PD-L1), microsatellite instability (MSI), and tumor mutational load (TMB), have been shown to correlate with immune efficacy in numerous studies and are increasingly employed for the selection of patients most likely to respond to immunotherapy. Gut microorganisms, genetic mutations like POLE/POLD1 and NOTCH4, tumor lymphoid infiltrating cells (TILs), and other novel biomarkers have the potential to develop into new predictors. Prospective immunotherapy for gastric cancer should be guided by a biomarker-driven precision management paradigm, and multidimensional or dynamic marker testing could be the way to go.
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Affiliation(s)
| | | | | | | | | | | | - Hong Qiu
- Department of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.L.)
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19
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Pei WG, Chen WZ, Wu YK, Tan SX, Jie ZG. Immune-related adverse events associated with immune checkpoint inhibitors for advanced gastric and gastroesophageal junction cancer: A meta-analysis. World J Gastrointest Oncol 2023; 15:352-367. [PMID: 36908315 PMCID: PMC9994050 DOI: 10.4251/wjgo.v15.i2.352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 10/23/2022] [Accepted: 11/29/2022] [Indexed: 02/14/2023] Open
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) have shown promising efficacy in treatment and clinical management of advanced gastric and gastroesophageal junction cancer. However, the inhibitors also cause immune-related adverse events (irAEs). The current systematic review and meta-analysis study aimed to investigate the incidence and nature of irAEs caused by ICIs.
AIM To investigate the incidence and nature of irAEs in advanced gastric and gastroesophageal junction cancer.
METHODS This systematic review was registered with PROSPERO (Reg. number: CRD42020152291). Data included in this study were collected from patients diagnosed with advanced gastric cancer or gastroesophageal junction cancer and treated with ICIs. A systematic literature search was conducted using the PubMed, EMBASE, and Cochrane Library databases. Meta-analysis was carried out using the single sample rate method. Synthesis and analysis of the data was conducted using Stata/SE and Review Manager Software.
RESULTS The patients enrolled in the present study included 14 patients from 14 case reports, 326 patients from 6 case series, and 1249 patients from 8 clinical trials. It was found that the overall incidence of irAEs was 16% [95% confidence interval (CI): 11-20] for all grades and 3% (95%CI: 2-4) for the severe grade. It was evident that the incidence of irAEs varied with the type of inhibitor and organs. A comparative study of the anti-programmed cell death receptor-1 (PD-1) and anti-programmed death receptor-ligand 1 (PD-L1) treatments showed that the anti-PD-1 group had a higher overall incidence of irAEs (20%) as compared with that of the anti-PD-L1 group (13%). Results of this study showed that the endocrine system experienced the highest incidence of organ-specific irAEs (7.4%), including hypothyroidism, hyperthyroidism, thyroiditis, diabetes, and adrenal insufficiency, followed by gastroenterology (2.2%), pulmonology (1.8%), neurology (1.4%), dermatology (1.4%), hematology (0.8%), and hepatology (0.7%). In clinical trials, it was found that the incidence of death related to irAEs was 1% (95%CI: 0-2.0), whereby colitis and interstitial lung diseases were the leading causes of death.
CONCLUSION It was evident that the incidence and nature of irAEs are both organ- and inhibitor-specific. The anti-PD-1 group had the highest incidence of all irAEs grades including the severe grades of irAEs. Early identification and management of irAEs allows clinical oncologists to effectively consider the pros and cons and hence enables them to strike a balance.
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Affiliation(s)
- Wen-Guang Pei
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Wen-Zheng Chen
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yu-Kang Wu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Sheng-Xing Tan
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zhi-Gang Jie
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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Wu YX, Zhou XY, Wang JQ, Chen GM, Chen JX, Wang RC, Huang JQ, Chen JS. Application of immune checkpoint inhibitors in immunotherapy for gastric cancer. Immunotherapy 2023; 15:101-115. [PMID: 36597704 DOI: 10.2217/imt-2022-0080] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Gastric cancer is the fifth most common cancer worldwide. With the development of immunotherapy, especially the application of immune checkpoint inhibitors (ICIs), the prognosis of advanced gastric cancer has improved. At present, ICIs combined with other therapies or dual ICI strategies in the treatment of advanced gastric cancer have shown clinical effectiveness and controllable safety. In addition, predictive biomarkers facilitate the precise selection of patients. Therefore, it is crucial to explore rational combinations and reliable predictive biomarkers for ICI therapy. This article reviews the recent advances in ICIs and relevant predictive biomarkers in the treatment of gastric cancer.
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Affiliation(s)
- Yi-Xiang Wu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Xiao-Yu Zhou
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jian-Qi Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Gao-Min Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jin-Xu Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Rong-Chang Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jiong-Qiang Huang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jing-Song Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
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21
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Li T, Liu T, Zhao L, Liu L, Zheng X, Wang J, Zhang F, Hu Y. Effectiveness and safety of anti-PD-1 monotherapy or combination therapy in Chinese advanced gastric cancer: A real-world study. Front Oncol 2023; 12:976078. [PMID: 36686795 PMCID: PMC9850086 DOI: 10.3389/fonc.2022.976078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 12/19/2022] [Indexed: 01/07/2023] Open
Abstract
Purpose Gastric cancer (GC) is one of the most frequently diagnosed cancers and one of the leading causes of cancer deaths worldwide, especially in eastern Asia and China. Anti-PD-1 immune checkpoint inhibitors, Pembrolizumab and Nivolumab, have been approved for the treatment of locally advanced or metastatic gastric or gastroesophageal junction cancer (GC/GEJC). Our study evaluated the effectiveness and safety of anti-PD-1-based treatment (monotherapy or combination therapy) in Chinese patients with advanced or metastatic GC/GEJCs in a real-world setting. Methods A retrospective cohort study was conducted, and 54 patients from May 31, 2015, to May 31, 2021, were included in our analysis, including 19 patients treated with anti-PD-1 monotherapy and 35 patients treated with anti-PD-1 combination therapy. Demographic and clinical information were evaluated. Clinical response, survival outcomes, and safety profile were measured and analyzed. Results Overall, the median overall survival (mOS) was 11.10 months (95% CI, 7.05-15.15), and the median progression-free survival (mPFS) was 3.93 months (95% CI, 2.47-5.39). Of the patients, 16.7% achieved a clinical response, and 72.2% achieved disease control. Prolonged overall survival (OS) and progression-free survival (PFS) and increased clinical response were observed in the combination group compared with the monotherapy group, although statistical significance was not reached. In subgroups with live metastases or elevated baseline neutrophil-to-lymphocyte ratio (NLR) levels, combination therapy outperformed anti-PD-1 alone in survival outcomes. Patients treated with anti-PD-1 monotherapy (n = 5, 26.3%) had fewer treatment-related adverse events (TRAEs) than those in the combination group (n = 22, 62.9%). There were also fewer patients with TRAEs of grades 3-5 with monotherapy (n = 2, 10.5%) than with combination therapy (n = 7, 20.0%). Pneumonitis in three patients was the only potential immune-related adverse event reported. Conclusions Anti-PD-1-based monotherapy and combination therapy showed favorable survival outcomes and manageable safety profiles in advanced or metastatic GC/GEJCs. In clinical treatment, immunotherapy should be an indispensable choice in the treatment strategy for GC/GEJC. Patients with a heavy tumor burden and more metastatic sites might benefit more from combination therapy. Elderly patients and patients with more treatment lines or high Eastern Cooperative Oncology Group (ECOG) performance scores might be more suitable for immune monotherapy, and some clinical benefits have been observed.
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Affiliation(s)
- Tao Li
- Graduate School, Medical School of Chinese People's Liberation Army (PLA), Beijing, China,Department of Oncology, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China,Chinese People's Liberation Army (PLA) Key Laboratory of Oncology, Key Laboratory for Tumor Targeting Therapy and Antibody Drugs, Ministry of Education, Beijing, China
| | - Tingting Liu
- Graduate School, Medical School of Chinese People's Liberation Army (PLA), Beijing, China,Department of Pulmonary and Critical Care Medicine, the Second Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Lei Zhao
- Institute of Translational Medicine, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Lu Liu
- Graduate School, Medical School of Chinese People's Liberation Army (PLA), Beijing, China,Department of Nutrition, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Xuan Zheng
- Graduate School, Medical School of Chinese People's Liberation Army (PLA), Beijing, China,Department of Oncology, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China,Chinese People's Liberation Army (PLA) Key Laboratory of Oncology, Key Laboratory for Tumor Targeting Therapy and Antibody Drugs, Ministry of Education, Beijing, China
| | - Jinliang Wang
- Graduate School, Medical School of Chinese People's Liberation Army (PLA), Beijing, China,Department of Oncology, The Fifth Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China,*Correspondence: Jinliang Wang, ; Fan Zhang, ; Yi Hu,
| | - Fan Zhang
- Graduate School, Medical School of Chinese People's Liberation Army (PLA), Beijing, China,Department of Oncology, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China,Chinese People's Liberation Army (PLA) Key Laboratory of Oncology, Key Laboratory for Tumor Targeting Therapy and Antibody Drugs, Ministry of Education, Beijing, China,*Correspondence: Jinliang Wang, ; Fan Zhang, ; Yi Hu,
| | - Yi Hu
- Graduate School, Medical School of Chinese People's Liberation Army (PLA), Beijing, China,Department of Oncology, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China,Chinese People's Liberation Army (PLA) Key Laboratory of Oncology, Key Laboratory for Tumor Targeting Therapy and Antibody Drugs, Ministry of Education, Beijing, China,*Correspondence: Jinliang Wang, ; Fan Zhang, ; Yi Hu,
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22
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Wang Q, Shen Z, Ge M, Xu J, Zhang X, Zhu W, Liu J, Hua W, Mao Y. Unexpected curative effect of PD-1 inhibitor in gastric cancer with brain metastasis: A case report. Front Oncol 2023; 13:1042417. [PMID: 36874117 PMCID: PMC9978328 DOI: 10.3389/fonc.2023.1042417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 02/02/2023] [Indexed: 02/18/2023] Open
Abstract
Background Gastric cancer (GC) is the third most common cause of cancer-related death in the world. Several clinical trials have proven that the use of PD-1/PD-L1 inhibitors can improve the survival of late-stage GC patients and is suggested in NCCN and CSCO guidelines. However, the correlation between PD-L1 expression and the response to PD-1/PD-L1 inhibitors is still controversial. GC rarely develops brain metastasis (BrM) and currently there is no therapeutic protocol for GC BrMs. Case presentation We report a case of a 46-year-old male suffering from GC with PD-L1 negative BrMs 12 years after GC resection and 5 cycles of chemotherapy. We treated the patient with the immune checkpoint inhibitor (ICI) pembrolizumab and all metastatic tumors achieved a complete response (CR). A durable remission of the tumors is confirmed after 4 years of follow-up. Conclusion We shared a rare case with PD-L1 negative GC BrM responsive to PD-1/PD-L1 inhibitors, the mechanism of which is still unclear. The protocol of therapeutic choice for late-stage GC with BrM is urgently needed. And we are expecting biomarkers other than PD-L1 expressions to predict the efficacy of ICI treatment.
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Affiliation(s)
- Qijun Wang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.,National Center for Neurological Disorders, Shanghai, China.,Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China.,Neurosurgical Institute of Fudan University, Shanghai, China.,Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Zhewei Shen
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.,National Center for Neurological Disorders, Shanghai, China.,Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China.,Neurosurgical Institute of Fudan University, Shanghai, China.,Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Mengxi Ge
- Department of Oncology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jie Xu
- Institute of Biomedical Sciences, Fudan University, Shanghai, China
| | - Xin Zhang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.,National Center for Neurological Disorders, Shanghai, China.,Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China.,Neurosurgical Institute of Fudan University, Shanghai, China.,Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Wei Zhu
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.,National Center for Neurological Disorders, Shanghai, China.,Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China.,Neurosurgical Institute of Fudan University, Shanghai, China.,Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Jie Liu
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Wei Hua
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.,National Center for Neurological Disorders, Shanghai, China.,Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China.,Neurosurgical Institute of Fudan University, Shanghai, China.,Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
| | - Ying Mao
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.,National Center for Neurological Disorders, Shanghai, China.,Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China.,Neurosurgical Institute of Fudan University, Shanghai, China.,Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
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23
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Zhang Z, Liu N, Sun M. Research Progress of Immunotherapy for Gastric Cancer. Technol Cancer Res Treat 2023; 22:15330338221150555. [PMID: 37042029 PMCID: PMC10102952 DOI: 10.1177/15330338221150555] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 10/16/2022] [Accepted: 12/22/2022] [Indexed: 04/13/2023] Open
Abstract
Gastric cancer (GC) is one of the most common gastrointestinal tract cancers worldwide, which has high incidence and mortality rates and poor prognosis. Although multidisciplinary comprehensive therapies consisting of surgery, chemotherapy, radiotherapy, and targeted therapy have made great progress in GC treatment, a satisfactory curative effect still cannot be achieved in many circumstances, and the 5-year survival of patients with GC remains to be very low. In China, about 75% of patients with GC are diagnosed in the advanced stage and thus miss the opportunity of surgical resection. Although the conventional treatment of GC has improved the survival time of advanced patients to a certain extent, the clinical efficacy has encountered a bottleneck and cannot bring higher survival benefits to patients. With the development of immunologic and molecular biologic technologies, immunotherapy has gradually become a new essential treatment for GC, which has attracted extensive attention in the field of oncology. The US Food and Drug Administration (USFDA) and China Food and Drug Administration (CFDA) have approved a variety of immune-related drugs for the treatment of GC, and all of which have achieved good efficacy. In this review, we summarize the recent development in nonspecific enhancer therapy, adoptive immunocell therapy, tumor vaccine therapy, oncolytic virus therapy, and immune checkpoint inhibitor therapy, and their roles in the treatment of GC.
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Affiliation(s)
- Zhipeng Zhang
- Key Laboratory of Liver and Kidney
Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai,
China
| | - Ningning Liu
- Department of Medical Oncology and
Cancer Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai,
China
| | - Mingyu Sun
- Key Laboratory of Liver and Kidney
Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai,
China
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24
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Shen J, Wang Z. Recent advances in the progress of immune checkpoint inhibitors in the treatment of advanced gastric cancer: A review. Front Oncol 2022; 12:934249. [PMID: 36505771 PMCID: PMC9730822 DOI: 10.3389/fonc.2022.934249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 11/04/2022] [Indexed: 11/25/2022] Open
Abstract
Most patients with advanced gastric cancer were treated with palliative therapy, which had a poor curative effect and a short survival time. In recent years, the clinical research of immune checkpoint inhibitors in advanced gastric cancer has made a breakthrough and has become an important treatment for advanced gastric cancer. The modes of immune checkpoint inhibitors in the treatment of advanced gastric cancer include single drug, combined chemotherapy, radiotherapy, and multiple immune drug combination therapy, among which combination therapy shows better clinical efficacy, and a large number of trials are currently exploring more effective combination therapy programs. In this paper, the new clinical research progress of immune checkpoint inhibitors in the treatment of advanced gastric cancer is reviewed, with an emphasis on combination therapy.
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Affiliation(s)
- Jingjing Shen
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Zhongming Wang
- Department of Radiation Oncology, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China
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25
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Chen M, Li C, Sun M, Li Y, Sun X. Recent developments in PD-1/PD-L1 blockade research for gastroesophageal malignancies. Front Immunol 2022; 13:1043517. [PMID: 36505480 PMCID: PMC9731511 DOI: 10.3389/fimmu.2022.1043517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 11/03/2022] [Indexed: 11/25/2022] Open
Abstract
Gastroesophageal cancers (GECs) comprise malignancies in the stomach, esophagus, and gastroesophageal junction. Despite ongoing improvements in chemoradiotherapy, the clinical outcomes of GEC have not significantly improved over the years, and treatment remains challenging. Immune checkpoint inhibitors (ICIs) have been the subject of clinical trials worldwide for several years. Encouraging results have been reported in different countries, but further research is required to apply ICIs in the clinical care of patients with GEC. This review summarizes completed and ongoing clinical trials with programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway blockers in GEC and current biomarkers used for predicting PD-1/PD-L1 blockade efficacy. This review captures the main findings of PD-1/PD-L1 antibodies combined with chemotherapy as an effective first-line treatment and a monotherapy in second-line or more treatment and in maintenance therapy. This review aims to provide insight that will help guide future research and clinical trials, thereby improving the outcomes of patients with GEC.
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Affiliation(s)
- Meng Chen
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Chenyan Li
- Department of Endocrinology and Metabolism, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Mingjun Sun
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yiling Li
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xuren Sun
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China,*Correspondence: Xuren Sun,
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26
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Lipid Nanoparticles for mRNA Delivery to Enhance Cancer Immunotherapy. Molecules 2022; 27:molecules27175607. [PMID: 36080373 PMCID: PMC9458026 DOI: 10.3390/molecules27175607] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/24/2022] [Accepted: 08/24/2022] [Indexed: 12/24/2022] Open
Abstract
Messenger RNA (mRNA) is being developed by researchers as a novel drug for the treatment or prevention of many diseases. However, to enable mRNA to fully exploit its effects in vivo, researchers need to develop safer and more effective mRNA delivery systems that improve mRNA stability and enhance the ability of cells to take up and release mRNA. To date, lipid nanoparticles are promising nanodrug carriers for tumor therapy, which can significantly improve the immunotherapeutic effects of conventional drugs by modulating mRNA delivery, and have attracted widespread interest in the biomedical field. This review focuses on the delivery of mRNA by lipid nanoparticles for cancer treatment. We summarize some common tumor immunotherapy and mRNA delivery strategies, describe the clinical advantages of lipid nanoparticles for mRNA delivery, and provide an outlook on the current challenges and future developments of this technology.
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27
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Principe DR, Kamath SD, Korc M, Munshi HG. The immune modifying effects of chemotherapy and advances in chemo-immunotherapy. Pharmacol Ther 2022; 236:108111. [PMID: 35016920 PMCID: PMC9271143 DOI: 10.1016/j.pharmthera.2022.108111] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 12/06/2021] [Accepted: 01/05/2022] [Indexed: 02/06/2023]
Abstract
Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for several malignancies. While the use of single-agent or combined ICIs has achieved acceptable disease control rates in a variety of solid tumors, such approaches have yet to show substantial therapeutic efficacy in select difficult-to-treat cancer types. Recently, select chemotherapy regimens are emerging as extensive modifiers of the tumor microenvironment, leading to the reprogramming of local immune responses. Accordingly, data is now emerging to suggest that certain anti-neoplastic agents modulate various immune cell processes, most notably the cross-presentation of tumor antigens, leukocyte trafficking, and cytokine biosynthesis. As such, the combination of ICIs and cytotoxic chemotherapy are beginning to show promise in many cancers that have long been considered poorly responsive to ICI-based immunotherapy. Here, we discuss past and present attempts to advance chemo-immunotherapy in these difficult-to-treat cancer histologies, mechanisms through which select chemotherapies modify tumor immunogenicity, as well as important considerations when designing such approaches to maximize efficacy and improve therapeutic response rates.
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Affiliation(s)
- Daniel R Principe
- Medical Scientist Training Program, University of Illinois College of Medicine, Chicago, IL, USA; Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.
| | - Suneel D Kamath
- Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA
| | - Murray Korc
- Department of Developmental and Cell Biology, University of California, Irvine, CA, USA
| | - Hidayatullah G Munshi
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Jesse Brown VA Medical Center, Chicago, IL, USA
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28
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Mak TK, Li X, Huang H, Wu K, Huang Z, He Y, Zhang C. The cancer-associated fibroblast-related signature predicts prognosis and indicates immune microenvironment infiltration in gastric cancer. Front Immunol 2022; 13:951214. [PMID: 35967313 PMCID: PMC9372353 DOI: 10.3389/fimmu.2022.951214] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 07/04/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common cancers, with a wide range of symptoms and outcomes. Cancer-associated fibroblasts (CAFs) are newly identified in the tumor microenvironment (TME) and associated with GC progression, prognosis, and treatment response. A novel CAF-associated prognostic model is urgently needed to improve treatment strategies. METHODS The detailed data of GC samples were downloaded from The Cancer Genome Atlas (TCGA), GSE62254, GSE26253, and GSE84437 datasets, then obtained 18 unique CAF-related genes from the research papers. Eight hundred eight individuals with GC were classified as TCGA or GSE84437 using consensus clustering by the selected CAF-related genes. The difference between the two subtypes revealed in this study was utilized to create the "CAF-related signature score" (CAFS-score) prognostic model and validated with the Gene Expression Omnibus (GEO) database. RESULTS We identified two CAF subtypes characterized by high and low CAFS-score in this study. GC patients in the low CAFS-score group had a better OS than those in the high CAFS-score group, and the cancer-related malignant pathways were more active in the high CAFS-score group, compared to the low CAFS-score group. We found that there was more early TNM stage in the low CAFS-score subgroup, while there was more advanced TNM stage in the high CAFS-score subgroup. The expression of TMB was significantly higher in the low CAFS-score subgroup than in the high CAFS-score subgroup. A low CAFS-score was linked to increased microsatellite instability-high (MSI-H), mutation load, and immunological activation. Furthermore, the CAFS-score was linked to the cancer stem cell (CSC) index as well as chemotherapeutic treatment sensitivity. The patients in the high CAFS-score subgroup had significantly higher proportions of monocytes, M2 macrophages, and resting mast cells, while plasma cells and follicular helper T cells were more abundant in the low-risk subgroup. The CAFS-score was also highly correlated with the sensitivity of chemotherapeutic drugs. The low CAFS-score group was more likely to have an immune response and respond to immunotherapy. We developed a nomogram to improve the CAFS-clinical score's usefulness. CONCLUSION The CAFS-score may have a significant role in the TME, clinicopathological characteristics, prognosis, CSC, MSI, and drug sensitivity, according to our investigation of CAFs in GC. We also analyzed the value of the CAFS-score in immune response and immunotherapy. This work provides a foundation for improving prognosis and responding to immunotherapy in patients with GC.
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Affiliation(s)
- Tsz Kin Mak
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Xing Li
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Huaping Huang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Kaiming Wu
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Zhijian Huang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Yulong He
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Changhua Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
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Li X, Xu J, Xie J, Yang W. Research progress in targeted therapy and immunotherapy for gastric cancer. Chin Med J (Engl) 2022; 135:1299-1313. [PMID: 35830242 PMCID: PMC9433086 DOI: 10.1097/cm9.0000000000002185] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Indexed: 11/26/2022] Open
Abstract
ABSTRACT Gastric cancer (GC) is one of the most common malignant tumors worldwide. Its incidence ranks the 5th among all malignant tumors globally, and it is the 3rd leading cause of death among patients with cancer. Surgical treatment is the first choice in clinical practice. However, targeted therapy, immunotherapy, and other treatment methods have also become research hotspots at home and abroad with the development of individualized precision therapy in recent years, besides traditional radiotherapy and chemotherapy. At present, targeted therapy and immunotherapy are methods used for treating GC, and they have important clinical application value and prospects. This study aimed to review the research progress of targeted therapy and immunotherapy for GC, focusing on its mechanism of action and related important clinical trials, hoping to provide references for the clinical treatment of GC.
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Affiliation(s)
- Xuewei Li
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Jun Xu
- Department of Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Jun Xie
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Wenhui Yang
- Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi 030032, China
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30
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304-1); waitfor delay '0:0:15' --] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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31
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304wpy7ghdo') or 847=(select 847 from pg_sleep(15))--] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.00000000000293040"xor(if(now()=sysdate(),sleep(15),0))xor"z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304'"] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304gtzafwi0'; waitfor delay '0:0:15' --] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.00000000000293040'xor(if(now()=sysdate(),sleep(15),0))xor'z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304" and 2*3*8=6*8 and "3ihd"="3ihd] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304' and 2*3*8=6*8 and 'c6mk'='c6mk] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304%' and 2*3*8=6*8 and 'ossv'!='ossv%] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304-1; waitfor delay '0:0:15' --] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 PMCID: PMC9276259 DOI: 10.1097/md.0000000000029304] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304dbecpiml')) or 922=(select 922 from pg_sleep(15))--] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304-1 waitfor delay '0:0:15' --] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304'||dbms_pipe.receive_message(chr(98)||chr(98)||chr(98),15)||'] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304����%2527%2522\'\"] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304mfck3a4e' or 943=(select 943 from pg_sleep(15))--] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.00000000000293048ib8fgtr')); waitfor delay '0:0:15' --] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304'||'] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.0000000000029304wgil3qmj] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore) 2022; 101:e29304. [PMID: 35623069 DOI: 10.1097/md.00000000000293044wyjc6pk'); waitfor delay '0:0:15' --] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/27/2022] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the fourth most common cause of cancer-related death worldwide. Most patients are diagnosed at later stage, because of few treatment options, the prognosis is poor. In recent years, however, Immune checkpoint inhibitors(ICIs), such as anti- programmed death-1 (PD-1), anti-PD-L1, and anti-cytotoxic T lymphocyte antigen 4, have emerged as promising therapeutic agents in GC. Here, we summary the current treatment and advances of immune checkpoint inhibitors in the advanced stage of GC. METHODS WANFANG MED ONLINE, CNKI, NCBI PUBMED and clinicaltrials.gov were used to search literature spanning from 2000 to 2021, and all literatures about "advanced gastric or gastro-oesophageal junction cancer, Immune checkpoint inhibitors, PD-1, PD-L1, Cytotoxic T lymphocyte antigen 4, immune therapy" with detailed data were included. RESULTS Nivolumab and pembrolizumab have been recommended for the third line or subsequent therapy in advanced GC. Nivolumab plus chemotherapy has been recommended for the first line treatment in advanced GC in China. Many other ICIs have been demonstrating encouraging efficacy. PD-L1, MSI-H, Epstein Barr virus, and tumor mutational burden (TMB) status maybe potential biomarkers for response to clinical outcomes for ICIs in GC. CONCLUSION ICIs have shown encouraging treatment efficacy and manageable safety profile in GC. Some biomarkers including PD-L1, MSI-H, EBV, and TMB status could evaluate the efficacy of ICIs in GC.
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Affiliation(s)
- Xiaojing Chang
- Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China
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Ma ES, Wang ZX, Zhu MQ, Zhao J. Immune evasion mechanisms and therapeutic strategies in gastric cancer. World J Gastrointest Oncol 2022; 14:216-229. [PMID: 35116112 PMCID: PMC8790417 DOI: 10.4251/wjgo.v14.i1.216] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/22/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is a malignancy with a high incidence and mortality. The tumor immune microenvironment plays an important role in promoting cancer development and supports GC progression. Accumulating evidence shows that GC cells can exert versatile mechanisms to remodel the tumor immune microenvironment and induce immune evasion. In this review, we systematically summarize the intricate crosstalk between GC cells and immune cells, including tumor-associated macrophages, neutrophils, myeloid-derived suppressor cells, natural killer cells, effector T cells, regulatory T cells, and B cells. We focus on how GC cells alter these immune cells to create an immunosuppressive microenvironment that protects GC cells from immune attack. We conclude by compiling the latest progression of immune checkpoint inhibitor-based immunotherapies, both alone and in combination with conventional therapies. Anti-cytotoxic T-lymphocyte-associated protein 4 and anti-programmed cell death protein 1/programmed death-ligand 1 therapy alone does not provide substantial clinical benefit for GC treatment. However, the combination of immune checkpoint inhibitors with chemotherapy or targeted therapy has promising survival advantages in refractory and advanced GC patients. This review provides a comprehensive understanding of the immune evasion mechanisms of GC, and highlights promising immunotherapeutic strategies.
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Affiliation(s)
- En-Si Ma
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
- Institute of Organ Transplantation, Fudan University, Shanghai 200040, China
| | - Zheng-Xin Wang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
- Institute of Organ Transplantation, Fudan University, Shanghai 200040, China
| | - Meng-Qi Zhu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Jing Zhao
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
- Cancer Metastasis Institute, Fudan University, Shanghai 200040, China
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