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Sun F, Gao X, Li T, Zhao X, Zhu Y. Tumor immune microenvironment remodeling after neoadjuvant therapy in gastric cancer: Update and new challenges. Biochim Biophys Acta Rev Cancer 2025; 1880:189350. [PMID: 40355011 DOI: 10.1016/j.bbcan.2025.189350] [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: 11/23/2024] [Revised: 05/05/2025] [Accepted: 05/08/2025] [Indexed: 05/14/2025]
Abstract
Gastric cancer (GC) is a malignant tumor with one of the highest morbidity and death rates in the world. Neoadjuvant therapy, including neoadjuvant chemotherapy (NAC) and NAC combined with immunotherapy, can improve the resection and long-term survival rates. However, not all patients respond well to neoadjuvant therapy. It has been confirmed that immune cells in the tumor immune microenvironment, including T cells, B cells, and natural killer cells, can affect the efficacy of neoadjuvant therapy. This paper summarizes current preclinical and clinical evidence to more fully describe the effects of neoadjuvant therapy on the immune microenvironment of GC, to provide the impetus to identify biomarkers to predict the potency of neoadjuvant therapy, and to identify the mechanisms of drug resistance, which should promote the development of individualized and accurate treatments for GC patients.
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Affiliation(s)
- Fujing Sun
- Department of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, China
| | - Xiaozhuo Gao
- Department of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, China
| | - Tianming Li
- Department of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, China
| | - Xiaoyan Zhao
- Graduate School, Dalian Medical University, Dalian, China
| | - Yanmei Zhu
- Department of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, China.
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2
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Adlakha YK, Chhabra R. The human microbiome: redefining cancer pathogenesis and therapy. Cancer Cell Int 2025; 25:165. [PMID: 40296128 PMCID: PMC12039184 DOI: 10.1186/s12935-025-03787-x] [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: 09/27/2024] [Accepted: 04/11/2025] [Indexed: 04/30/2025] Open
Abstract
The human microbiome has always been an important determinant of health and recently, its role has also been described in cancer. The altered microbiome could aid cancer progression, modulate chemoresistance and significantly alter drug efficacy. The broad implications of microbes in cancer have prompted researchers to investigate the microbe-cancer axis and identify whether modifying the microbiome could sensitize cancer cells for therapy and improve the survival outcome of cancer patients. The preclinical data has shown that enhancing the number of specific microbial species could restore the patients' response to cancer drugs and the microbial biomarkers may play a vital role in cancer diagnostics. The elucidation of detailed interactions of the human microbiota with cancer would not only help identify the novel drug targets but would also enhance the efficacy of existing drugs. The field exploring the emerging roles of microbiome in cancer is at a nascent stage and an in-depth scientific perspective on this topic would make it more accessible to a wider audience. In this review, we discuss the scientific evidence connecting the human microbiome to the origin and progression of cancer. We also discuss the potential mechanisms by which microbiota affects initiation of cancer, metastasis and chemoresistance. We highlight the significance of the microbiome in therapeutic outcome and evaluate the potential of microbe-based cancer therapy.
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Affiliation(s)
- Yogita K Adlakha
- Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Sector-125, Noida, Uttar Pradesh, 201303, India.
| | - Ravindresh Chhabra
- Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Ghudda, Bathinda, 151401, Punjab, India.
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3
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Wu J, Liang J, Li S, Lu J, Li Y, Zhang B, Gao M, Zhou J, Zhang Y, Chen J. Cancer vaccine designed from homologous ferritin-based fusion protein with enhanced DC-T cell crosstalk for durable adaptive immunity against tumors. Bioact Mater 2025; 46:516-530. [PMID: 39868073 PMCID: PMC11764028 DOI: 10.1016/j.bioactmat.2024.12.029] [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: 07/05/2024] [Revised: 09/30/2024] [Accepted: 12/27/2024] [Indexed: 01/28/2025] Open
Abstract
Peptide vaccines based on tumor antigens face the challenges of rapid clearance of peptides, low immunogenicity, and immune suppressive tumor microenvironment. However, the traditional solution mainly uses exogenous substances as adjuvants or carriers to enhance innate immune responses, but excessive inflammation can damage adaptive immunity. In the current study, we propose a straightforward novel nanovaccine strategy by employing homologous human ferritin light chain for minimized innate immunity and dendritic cell (DC) targeting, the cationic KALA peptide for enhanced cellular uptake, and suppressor of cytokine signaling 1 (SOCS1) siRNA for modulating DC activity. Upon fusing with the KALA peptide, this nanovaccine presents as a novel 40-mer cage structure, with highly enriched antigen peptides of proper size (25 nm) for targeted delivery to lymph nodes. The loading of SOCS1 siRNA onto the KALA peptide promoted DC maturation in tumor environment, leading to a 3-fold increase in antigen presentation compared to alum adjuvant. Moreover, it demonstrates remarkable efficacy in suppressing tumor progression and metastasis, together with prolonged survival. In addition, the nanovaccine stimulates up to 40 % memory T cells, thereby achieving sustained protection against tumor re-challenge. This unprecedented nanovaccine platform can ignite fresh interdisciplinary discussions on interactive strategies for future peptide vaccine development.
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Affiliation(s)
- Jun Wu
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
- School of Chemical & Material Engineering, Jiangnan University, Wuxi, 214122, PR China
| | - Jing Liang
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
| | - Sichen Li
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
| | - Jinjin Lu
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
| | - Yi Li
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
| | - Bin Zhang
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
| | - Min Gao
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
| | - Juan Zhou
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
| | - Yan Zhang
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
| | - Jinghua Chen
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China
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Portillo-Miño JD, Calderon JJ, Riquelme A. BTK inhibitors are a possible emerging therapeutic target for gastric cancer. MOLECULAR THERAPY. ONCOLOGY 2025; 33:200935. [PMID: 39990595 PMCID: PMC11846545 DOI: 10.1016/j.omton.2025.200935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Affiliation(s)
- José Darío Portillo-Miño
- Infectious Diseases and Cancer Research Group (GINFYCA), Clinical Research Center, Fundación Hospital San Pedro, Pasto, Nariño, Colombia
- Colombian Research Group on Helicobacter pylori, Bogota, Colombia
| | - Jhon Jairo Calderon
- Grupo de Inmunobiologia y Biologia Celular, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogota, Colombia
| | - Arnoldo Riquelme
- Department of Gastroenterology, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile
- Centro para el Control y Prevencion del Cancer (CECAN), Santiago, Chile
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5
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Chen Z, Ma Y, Chen J. Applications and challenges of immunotherapy in the management of gastric adenocarcinoma: current status and future perspectives. World J Surg Oncol 2025; 23:92. [PMID: 40108691 PMCID: PMC11921727 DOI: 10.1186/s12957-025-03752-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 03/13/2025] [Indexed: 03/22/2025] Open
Abstract
Gastric adenocarcinoma (GAC) remains a significant global public health challenge, characterized by high incidence and mortality rates. Progress in tumor immunology has introduced immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways, demonstrating substantial potential in GAC therapy. Clinical research indicates that ICIs, particularly when combined with chemotherapy or targeted therapies, significantly enhance treatment efficacy in advanced GAC and specific molecular subtypes, including microsatellite instability-high (MSI-H) and human epidermal growth factor receptor 2 (HER2)-positive patients. However, immunotherapy is also associated with a range of immune-related adverse events (irAEs), necessitating effective management strategies to ensure treatment safety and maintain patients' quality of life. Future studies should focus on identifying new therapeutic targets, optimizing patient selection, and developing personalized treatment approaches to further improve the efficacy and safety of immunotherapy in GAC.
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Affiliation(s)
- Zhiyao Chen
- Department of Gastrointestinal & Esophageal Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yunbin Ma
- Department of General surgery, Yiling Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jianan Chen
- Department of Clinical Sciences, H. Lee Moffitt Cancer Center & Research Institute, 12902 USF Magnolia Drive, Tampa, FL, USA.
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6
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Yun H, Dong F, Wei X, Yan X, Zhang R, Zhang X, Wang Y. Role and value of the tumor microenvironment in the progression and treatment resistance of gastric cancer (Review). Oncol Rep 2025; 53:14. [PMID: 39611496 PMCID: PMC11622107 DOI: 10.3892/or.2024.8847] [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: 08/08/2024] [Accepted: 10/08/2024] [Indexed: 11/30/2024] Open
Abstract
Gastric cancer (GC) is characterized by a complex and heterogeneous tumor microenvironment (TME) that significantly influences disease progression and treatment outcomes. The tumor stroma, which is composed of a variety of cell types such as cancer‑associated fibroblasts, immune cells and vascular components, displays significant spatial and temporal diversity. These stromal elements engage in dynamic crosstalk with cancer cells, shaping their proliferative, invasive and metastatic potential. Furthermore, the TME is instrumental in facilitating resistance to traditional chemotherapy, specific treatments and immunotherapy strategies. Understanding the underlying mechanisms by which the GC microenvironment evolves and supports tumor growth and therapeutic resistance is critical for developing effective treatment strategies. The present review explores the latest progress in understanding the intricate interactions between cancer cells and their immediate environment in GC, highlighting the implications for disease pathogenesis and therapeutic interventions.
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Affiliation(s)
- Heng Yun
- Department of General Surgery, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Baiyin, Gansu 730900, P.R. China
| | - Fangde Dong
- Department of General Surgery, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Baiyin, Gansu 730900, P.R. China
| | - Xiaoqin Wei
- Department of Pain, The Second People's Hospital of Baiyin, Baiyin, Gansu 730900, P.R. China
| | - Xinyong Yan
- Department of Proctology, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Baiyin, Gansu 730900, P.R. China
| | - Ronglong Zhang
- Department of General Surgery, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Baiyin, Gansu 730900, P.R. China
| | - Xiuyu Zhang
- Department of Gastroenterology, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Baiyin, Gansu 730900, P.R. China
| | - Yulin Wang
- Department of General Surgery, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Baiyin, Gansu 730900, P.R. China
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7
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Herdan RA, Taher MG, Shafiq AM, Omran OM, Abozaid L, Babiker N, AlQahtani SA, Taha NM, Taha NM, Shubaili AAY, Khubrani SAA, Ameen MG. Evaluation of the relationship between H. Pylori-infected gastric mucosa and prognosis of gastrointestinal stromal tumor. Int J Health Sci (Qassim) 2025; 19:41-48. [PMID: 39760053 PMCID: PMC11699233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025] Open
Abstract
Objective Gastrointestinal stromal tumor (GIST) is the most common type of mesenchymal tumor accounting for 2.2% of all malignant gastric tumors. Mesenchymal stem cells (MSCs) play crucial roles in gastric carcinogenesis. In addition, Helicobacter pylori has been linked to GIST as it induces an epithelial response that can home MSCs to the stomach mucosa. This study aimed to investigate the relationship between H. pylori-infected gastric mucosa and the development of CD117-positive GIST and evaluate the prognosis of H. pylori-infected gastric mucosa of GIST patients that received anti-CD117 therapy. Methods This is a retrospective study conducted on H. pylori-infected GIST patients diagnosed between 2015 and 2021. The follow-up period was performed for a minimum of 2 years. Clinicopathological factors for each patient were collected from cases selected from the Registry of Pathology and Surgery Departments at Assiut University Hospitals. Results There was a statistically significant difference between our study population regarding the overall survival of studied patients, disease-free survival of studied patients, and the relationship between H. pylori-infected gastric mucosa and development, grading, therapy response, and overall survival of GIST except in status at last follow-up. Conclusions Our study is the first to reveal that H. pylori infection is linked to a worse prognosis for GIST patients. H. pylori has the potential to be used as a strong predictive biomarker for GIST individuals in the future. Clinical research with large samples as well as prospective designs are needed to confirm this connection.
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Affiliation(s)
- Rania A. Herdan
- Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Mohamed Gamal Taher
- Department of General Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ahmed Mahran Shafiq
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Ola M. Omran
- Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Pathology, College of Medicine, Qassim University, Buridah, Qassim Region, Saudi Arabia
| | - Lobaina Abozaid
- Department of Pathology, College of Medicine, Qassim University, Buridah, Qassim Region, Saudi Arabia
| | - Nahla Babiker
- Department of Pathology, College of Medicine, Qassim University, Buridah, Qassim Region, Saudi Arabia
| | - Saeed A. AlQahtani
- Department of Clinical Practice, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
| | - Nada M. Taha
- Medical Student, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Noha M. Taha
- Medical Student, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Aisha Ahmed Y. Shubaili
- Department of Medical laboratory King Khalid University Medical city, Abha 62223, Saudi Arabia
| | | | - Mahmoud Gamal Ameen
- Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
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Zeng Z, Sun Y, Jiang J, Xu X, Lin H, Li W, Zheng D, Huang Y, Zhao C. Engineered low-pathogenic Helicobacter pylori as orally tumor immunomodulators for the stimulation of systemic immune response. Biomaterials 2024; 311:122672. [PMID: 38897029 DOI: 10.1016/j.biomaterials.2024.122672] [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: 02/16/2024] [Revised: 05/14/2024] [Accepted: 06/15/2024] [Indexed: 06/21/2024]
Abstract
Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori (H. pylori) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori. H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori-based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy.
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Affiliation(s)
- Zishan Zeng
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Yue Sun
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Jingwen Jiang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Xiaoyu Xu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Huanxin Lin
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Wanzhen Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Dong Zheng
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Yanjuan Huang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Chunshun Zhao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China.
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Banisefid E, Nasiri E, Pourebrahimian Leilabadi S, Hamzehzadeh S, Akbarzadeh MA, Hosseini MS. The paradox of Helicobacter pylori: how does H. pylori infection protect against esophageal cancer? Ann Med Surg (Lond) 2024; 86:7221-7226. [PMID: 39649904 PMCID: PMC11623814 DOI: 10.1097/ms9.0000000000002674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 10/10/2024] [Indexed: 12/11/2024] Open
Abstract
Helicobacter pylori is a microaerophilic gram-negative bacterium infecting around half of the world's population. Despite its well-known role in gastric malignancies, its impact on esophageal cancer comes with a complex paradox. Several mechanisms have been proposed to explain its observed lack of carcinogenic activity in the esophagus, including the trigger of anti-inflammatory pathways, promoting atrophic gastritis, and esophageal microbiome modulation. However, recent studies have highlighted a significantly more complicated interplay, where H. pylori, typically considered a pathogen, may even deliver a protective effect against esophageal carcinogenesis. This paper aims to evaluate the prevalence of H. pylori infection among patients with esophageal carcinoma, discussing the underlying mechanisms of the paradoxical effects of H. pylori on esophageal cancer.
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Affiliation(s)
- Erfan Banisefid
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ehsan Nasiri
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Sina Hamzehzadeh
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Medical Philosophy and History Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Amin Akbarzadeh
- Research Center for Evidence-Based Medicine, Iranian EBM Center: A JBI Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad-Salar Hosseini
- Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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10
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Liu Y, Shang X, Du W, Shen W, Zhu Y. Helicobacter Pylori Infection as the Predominant High-Risk Factor for Gastric Cancer Recurrence Post-Gastrectomy: An 8-Year Multicenter Retrospective Study. Int J Gen Med 2024; 17:4999-5014. [PMID: 39494357 PMCID: PMC11531290 DOI: 10.2147/ijgm.s485347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 10/24/2024] [Indexed: 11/05/2024] Open
Abstract
Purpose The reappearance of gastric cancer, a frequent postoperative complication following radical gastric cancer surgery, substantially impacts the near-term and far-reaching medical outlook of patients. The objective of this research was to create a machine learning algorithm that could recognize high-risk factors for gastric cancer recurrence and anticipate the correlation between gastric cancer recurrence and Helicobacter pylori (H. pylori) infection. Patients and Methods This investigation comprised 1234 patients diagnosed with gastric cancer, and 37 characteristic variables were obtained. Four machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), k-nearest neighbor algorithm (KNN), and multilayer perceptron (MLP), were implemented to develop the models. The k-fold cross-validation technique was utilized to perform internal validation of the four models, while independent datasets were employed for external validation of the models. Results In contrast to the other machine learning models, the XGBoost algorithm demonstrated superior predictive ability regarding high-risk factors for gastric cancer recurrence. The outcomes of Shapley additive explanation (SHAP) analysis revealed that tumor invasion depth, tumor lymph node metastasis, H. pylori infection, postoperative carcinoembryonic antigen (CEA), tumor size, and tumor number were risk elements for gastric cancer recurrence in patients, with H. pylori infection being the primary high-risk factor. Conclusion Out of the four machine learning models, the XGBoost algorithm exhibited superior performance in predicting the recurrence of gastric cancer. In addition, machine learning models can help clinicians identify key prognostic factors that are clinically meaningful for the application of personalized patient monitoring and immunotherapy.
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Affiliation(s)
- Yuan Liu
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
- Department of General Surgery, Tengzhou Central People’s Hospital, Jining Medical College, Shandong, People’s Republic of China
| | - Xingchen Shang
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
| | - Wenyi Du
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
| | - Wei Shen
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
| | - Yanfei Zhu
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
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11
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Liu C, Fu L, Wang Y, Yang W. Influence of the gut microbiota on immune cell interactions and cancer treatment. J Transl Med 2024; 22:939. [PMID: 39407240 PMCID: PMC11476117 DOI: 10.1186/s12967-024-05709-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
The tumour microenvironment represents a novel frontier in oncological research. Over the past decade, accumulating evidence has underscored the importance of the tumour microenvironment (TME), including tumour cells, stromal cells, immune cells, and various secreted factors, which collectively influence tumour growth, invasion, and responses to therapeutic agents. Immune cells within the TME are now widely acknowledged to play pivotal roles in tumour development and treatment. While some perspectives have posited that immune cells within the TME facilitate tumour progression and confer resistance to therapeutic interventions, contrasting conclusions also exist. Affirmative and negative conclusions appear to be context dependent, and a unified consensus has yet to be reached. The burgeoning body of research on the relationship between the gut microbiota and tumours in recent years has led to a growing understanding. Most studies have indicated that specific components of the gut microbiota, such as unique bacterial communities or specific secretory factors, play diverse roles in regulating immune cells within the TME, thereby influencing the prognosis and outcomes of cancer treatments. A detailed understanding of these factors could provide novel insights into the TME and cancer therapy. In this study, we aimed to synthesise information on the interactions between the gut microbiota and immune cells within the TME, providing an in-depth exploration of the potential guiding implications for future cancer therapies.
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Affiliation(s)
- Chunxiao Liu
- Department of Gastroenterological Surgery, Hengqin Hospital, First Affiliated Hospital of Guangzhou Medical University, No. 118 Baoxing Road, Hengqin, Guangdong, 519031, China
| | - Lingfeng Fu
- Department of Gastroenterological Surgery, Hengqin Hospital, First Affiliated Hospital of Guangzhou Medical University, No. 118 Baoxing Road, Hengqin, Guangdong, 519031, China
| | - Yuxin Wang
- Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, Guangdong, 510515, China.
- Central Laboratory, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
| | - Weijun Yang
- Department of Gastroenterological Surgery, Hengqin Hospital, First Affiliated Hospital of Guangzhou Medical University, No. 118 Baoxing Road, Hengqin, Guangdong, 519031, China.
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12
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Zhao SQ, Zheng HL, Zhong XT, Wang ZY, Su Y, Shi YY. Effects and mechanisms of Helicobacter pylori infection on the occurrence of extra-gastric tumors. World J Gastroenterol 2024; 30:4090-4103. [DOI: 10.3748/wjg.v30.i37.4090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 08/23/2024] [Accepted: 09/12/2024] [Indexed: 09/26/2024] Open
Abstract
Helicobacter pylori (H. pylori) colonizes the human stomach and many studies have discussed the mechanisms of H. pylori infection leading to gastric diseases, including gastric cancer. Additionally, increasing data have shown that the infection of H. pylori may contribute to the development of extra-gastric diseases and tumors. Inflammation, systemic immune responses, microbiome disorders, and hypergastrinemia caused by H. pylori infection are associated with many extra-gastric malignancies. This review highlights recent discoveries; discusses the relationship between H. pylori and various extra-gastric tumors, such as colorectal cancer, lung cancer, cholangiocarcinoma, and gallbladder carcinoma; and explores the mechanisms of extra-gastric carcinogenesis by H. pylori. Overall, these findings refine our understanding of the pathogenic processes of H. pylori, provide guidance for the clinical treatment and management of H. pylori-related extra-gastric tumors, and help improve prognosis.
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Affiliation(s)
- Shi-Qing Zhao
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Hui-Ling Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Xiao-Tian Zhong
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Zi-Ye Wang
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Yi Su
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
- Health Science Center, Peking University, Beijing 100191, China
| | - Yan-Yan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
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13
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Zhong X, Zheng H, Zhao S, Wang Z, Su Y, Zhong K, Wang M, Shi Y. Effects and mechanisms of Helicobacter pylori on cancers development and immunotherapy. Front Immunol 2024; 15:1469096. [PMID: 39434880 PMCID: PMC11491387 DOI: 10.3389/fimmu.2024.1469096] [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: 07/23/2024] [Accepted: 09/23/2024] [Indexed: 10/23/2024] Open
Abstract
Tumor immunotherapy has been widely used in clinical treatment of various cancers. However, some patients of these cancers do not respond to immunotherapy effectively. And H. pylori infection has been considered to be related to the efficacy of immunotherapy. This review aims to summarize the different effects and mechanisms of H. pylori infection on immunotherapy in different kinds of cancers. We searched the relevant literature on H. pylori and tumor immunotherapy, and summarized to form a review. Generally, H. pylori infection plays a role in affecting kinds of cancers' development, besides gastric cancer. Current evidence suggests that H. pylori infection may reduce the efficacy of immunotherapy for colorectal cancer, non-small cell lung cancer and melanoma, but due to the lack of sufficient evidence, more data is needed to prove that. While for gastric cancer, the effects remain controversial. The H. pylori regulation effects and metabolisms involved in systematic related cancers should be paid attention to. Whether H. pylori should be eradicated when immunotherapy performed may be a critical consideration for some kinds of tumors.
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Affiliation(s)
- Xiaotian Zhong
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Huiling Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Shiqing Zhao
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Ziye Wang
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Yi Su
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Kaili Zhong
- Department of Lymphoma, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Mopei Wang
- Department of Tumor Chemotherapy and Radiation Sickness, Peking University Third Hospital, Beijing, China
| | - Yanyan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
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14
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Wang X, Zhao G, Shao S, Yao Y. Helicobacter pylori triggers inflammation and oncogenic transformation by perturbing the immune microenvironment. Biochim Biophys Acta Rev Cancer 2024; 1879:189139. [PMID: 38897421 DOI: 10.1016/j.bbcan.2024.189139] [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: 04/08/2024] [Revised: 06/09/2024] [Accepted: 06/14/2024] [Indexed: 06/21/2024]
Abstract
The immune microenvironment plays a critical regulatory role in the pathogenesis of Helicobacter pylori (H. pylori). Understanding the mechanisms that drive the transition from chronic inflammation to cancer may provide new insights for early detection of gastric cancer. Although chronic inflammation is frequent in precancerous gastric conditions, the monitoring function of the inflammatory microenvironment in the progression from H. pylori-induced chronic inflammation to gastric cancer remains unclear. This literature review summarizes significant findings on how H. pylori triggers inflammatory responses and facilitates cancer development through the immune microenvironment. Furthermore, the implications for future research and clinical applications are also addressed. The review is divided into four main sections: inflammatory response and immune evasion mechanisms induced by H. pylori, immune dysregulation associated with gastric cancer, therapeutic implications, and future perspectives on H. pylori-induced gastric carcinogenesis with a focus on the immune microenvironment.
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Affiliation(s)
- Xiuping Wang
- Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, China
| | - Guang Zhao
- Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, China; Department of Emergency Medicine, Kunshan Hospital Affiliated to Jiangsu University, Kunshan 215300, Jiangsu, China
| | - Shihe Shao
- School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
| | - Yongliang Yao
- Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu, China.
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15
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Wang X, Jiang D, Zhang X, Wang R, Yang F, Xie C. Causal associations between Helicobacter Pylori infection and the risk and symptoms of Parkinson's disease: a Mendelian randomization study. Front Immunol 2024; 15:1412157. [PMID: 39165356 PMCID: PMC11333313 DOI: 10.3389/fimmu.2024.1412157] [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: 04/04/2024] [Accepted: 07/22/2024] [Indexed: 08/22/2024] Open
Abstract
Background Increasing evidence suggests an association between Helicobacter pylori (HP) infection and Parkinson's disease (PD) and its clinical manifestations, but the causal relationship remain largely unknown. Objective To investigate the causal relationship between HP infection and PD risk, PD symptoms, and secondary parkinsonism, we conducted two-sample Mendelian randomization (MR). Methods We obtained summary data from genome-wide association studies for seven different antibodies specific to HP proteins and five PD-related phenotypes. The inverse-variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods were used to assess the causal relationships. Sensitivity analyses were performed to examine the stability of the MR results and reverse MR analysis was conducted to evaluate the presence of reverse causality. Results Genetically predicted HP antibodies were not causally associated with an increased risk of PD. However, HP cytotoxin-associated gene-A (CagA) and outer membrane protein (OMP) antibody level were causally associated with PD motor subtype (tremor to postural instability/gait difficulty score ratio; β = -0.16 and 0.46, P = 0.002 and 0.048, respectively). HP vacuolating cytotoxin-A (VacA) antibody level was causally associated with an increased risk of PD dementia [odds ratio (OR) = 1.93, P = 0.040]. Additionally, HP OMP antibody level was identified as a risk factor for drug-induced secondary parkinsonism (OR = 2.08, P = 0.033). These results were stable, showed no evidence of heterogeneity or directional pleiotropy, and no evidence of a reverse causal relationship. Conclusions Our findings indicate that HP infection does not increase the risk of PD, but contributes to PD motor and cognitive symptoms. Different types of HP antibodies affect different symptoms of PD. Eradication of HP infection may help modulate and improve symptoms in PD patients.
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Affiliation(s)
- Xin Wang
- Department of Neurology, Beijing Huairou Hospital of Traditional Chinese Medicine, Beijing, China
| | - Deming Jiang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xiao Zhang
- Department of Neurology, Beijing Huairou Hospital of Traditional Chinese Medicine, Beijing, China
| | - Ran Wang
- Department of Neurology, Beijing Huairou Hospital of Traditional Chinese Medicine, Beijing, China
| | - Fengyi Yang
- Department of Neurology, Beijing Huairou Hospital of Traditional Chinese Medicine, Beijing, China
| | - Chunrong Xie
- Department of Neurology, Beijing Huairou Hospital of Traditional Chinese Medicine, Beijing, China
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16
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Zhou Y, Liu S, Zheng Y, Wang Y, Zhou Y. The role of THBS1 and PDGFD in the immune microenvironment of Helicobacter pylori-associated gastric cancer. Arab J Gastroenterol 2024; 25:194-204. [PMID: 38705811 DOI: 10.1016/j.ajg.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/28/2023] [Accepted: 02/09/2024] [Indexed: 05/07/2024]
Abstract
BACKGROUND AND STUDY AIMS Immunotherapy has emerged as a hot topic in cancer treatment in recent years and has also shown potential in the treatment of Helicobacter pylori-associated gastric cancer. However, there is still a need to identify potential immunotherapy targets. MATERIAL AND METHODS We used the GSE116312 dataset of Helicobacter pylori-associated gastric cancer to identify differentially expressed genes, which were then overlapped with immune genes from the ImmPort database. The identified immune genes were used to classify gastric cancer samples and evaluate the relationship between classification and tumor mutations, as well as immune infiltration. An immune gene-based prognostic model was constructed, and the expression levels of the genes involved in constructing the model were explored in the tumor immune microenvironment. RESULTS We successfully identified 60 immune genes and classified gastric cancer samples into two subtypes, which showed differences in prognosis, tumor mutations, immune checkpoint expression, and immune cell infiltration. Subsequently, we constructed an immune prognostic model consisting of THBS1 and PDGFD, which showed significant associations with macrophages and fibroblasts. CONCLUSION We identified abnormal expression of THBS1 and PDGFD in cancer-associated fibroblasts (CAFs) within the tumor immune microenvironment, suggesting their potential as therapeutic targets.
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Affiliation(s)
- Yun Zhou
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China; Department of Geriatrics Gerontology, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Shixiong Liu
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China; Department of Geriatrics Gerontology, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Ya Zheng
- Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China; Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Yuping Wang
- Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China; Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China.
| | - Yongning Zhou
- Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China; Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China.
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17
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Zhou J, Zhang M, Wang H, Zhong X, Yang X. Role of Helicobacter pylori virulence factors and alteration of the Tumor Immune Microenvironment: challenges and opportunities for Cancer Immunotherapy. Arch Microbiol 2024; 206:167. [PMID: 38485861 DOI: 10.1007/s00203-024-03908-6] [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: 01/24/2024] [Revised: 02/19/2024] [Accepted: 02/22/2024] [Indexed: 03/19/2024]
Abstract
Various forms of malignancies have been linked to Helicobacter pylori. Despite advancements in chemotherapeutic and surgical approaches, the management of cancer, particularly at advanced stages, increasingly relies on the integration of immunotherapy. As a novel, safe therapeutic modality, immunotherapy harnesses the immune system of the patient to treat cancer, thereby broadening treatment options. However, there is evidence that H. pylori infection may influence the effectiveness of immunotherapy in various types of cancer. This association is related to H. pylori virulence factors and the tumor microenvironment. This review discusses the influence of H. pylori infection on immunotherapy in non-gastrointestinal and gastrointestinal tumors, the mechanisms underlying this relationship, and directions for the development of improved immunotherapy strategies.
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Affiliation(s)
- Junyi Zhou
- Department of Oncology, The Huai'an Clinical College of Xuzhou Medical University, Huai'an, Jiangsu, China
| | - Minna Zhang
- Department of Gastroenterology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China
| | - HongGang Wang
- Department of Gastroenterology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China
| | - Xiaomin Zhong
- Department of Oncology, The Huai'an Clinical College of Xuzhou Medical University, Huai'an, Jiangsu, China.
| | - XiaoZhong Yang
- Department of Gastroenterology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
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18
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Fan J, Zhu J, Xu H. Strategies of Helicobacter pylori in evading host innate and adaptive immunity: insights and prospects for therapeutic targeting. Front Cell Infect Microbiol 2024; 14:1342913. [PMID: 38469348 PMCID: PMC10925771 DOI: 10.3389/fcimb.2024.1342913] [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: 11/22/2023] [Accepted: 02/08/2024] [Indexed: 03/13/2024] Open
Abstract
Helicobacter pylori (H. pylori) is the predominant pathogen causing chronic gastric mucosal infections globally. During the period from 2011 to 2022, the global prevalence of H. pylori infection was estimated at 43.1%, while in China, it was slightly higher at approximately 44.2%. Persistent colonization by H. pylori can lead to gastritis, peptic ulcers, and malignancies such as mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas. Despite eliciting robust immune responses from the host, H. pylori thrives in the gastric mucosa by modulating host immunity, particularly by altering the functions of innate and adaptive immune cells, and dampening inflammatory responses adverse to its survival, posing challenges to clinical management. The interaction between H. pylori and host immune defenses is intricate, involving evasion of host recognition by modifying surface molecules, manipulating macrophage functionality, and modulating T cell responses to evade immune surveillance. This review analyzes the immunopathogenic and immune evasion mechanisms of H. pylori, underscoring the importance of identifying new therapeutic targets and developing effective treatment strategies, and discusses how the development of vaccines against H. pylori offers new hope for eradicating such infections.
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Affiliation(s)
- Jiawei Fan
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Jianshu Zhu
- Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China
| | - Hong Xu
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
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19
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Yang S, Hao S, Ye H, Zhang X. Cross-talk between Helicobacter pylori and gastric cancer: a scientometric analysis. Front Cell Infect Microbiol 2024; 14:1353094. [PMID: 38357448 PMCID: PMC10864449 DOI: 10.3389/fcimb.2024.1353094] [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: 12/09/2023] [Accepted: 01/17/2024] [Indexed: 02/16/2024] Open
Abstract
Background Helicobacter pylori (HP) is considered a leading risk factor for gastric cancer (GC). The aim of this article is to conduct bibliometric and visual analysis to assess scientific output, identify highly cited papers, summarize current knowledge, and explore recent hotspots and trends in HP/GC research. Methods A bibliographic search was conducted on October 24, 2023, to retrieve relevant studies on HP/GC research between 2003 and 2022. The search terms were attached to HP and GC. The main data were from the Web of Science Core Collection (WoSCC). Data visualization was performed using Biblioshiny, VOSviewer, and Microsoft Excel. Results In HP/GC research, 1970 papers were retrieved. The total number of papers (Np) in HP/GC was growing from 2003 to 2022. China and Japan were in the leading position and made the most contributions to HP/GC. Vanderbilt University and the US Department of Veterans Affairs had the highest Np. The most productive authors were Peek Jr Richard M. and Piazuelo M Blanca. Helicobacter received the most Np, while Gastroenterology had the most total citations (TC). High-cited publications and keyword clustering were used to identify the current status and trends in HP/GC research, while historical citation analysis provided insight into the evolution of HP/GC research. The hot topics included the effect of HP on gastric tumorigenesis and progression, the pathogenesis of HP-induced GC (HP factors), and the mechanisms by which HP affects GC (host factors). Research in the coming years could focus on topics such as autophagy, gut microbiota, immunotherapy, exosomes, epithelial-mesenchymal transition (EMT), and gamma-glutamyl transpeptidase (GGT). Conclusion This study evaluated the global scientific output in HP/GC research and its quantitative characteristics, identified the essential works, and collected information on the current status, main focuses and emerging trends in HP/GC research to provide academics with guidance for future paths.
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Affiliation(s)
- Shanshan Yang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
| | - Shaodong Hao
- Spleen-Stomach Department, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Ye
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
| | - Xuezhi Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
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20
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Wei BR, Zhao YJ, Cheng YF, Huang C, Zhang F. Helicobacter pylori infection and Parkinson's Disease: etiology, pathogenesis and levodopa bioavailability. Immun Ageing 2024; 21:1. [PMID: 38166953 PMCID: PMC10759355 DOI: 10.1186/s12979-023-00404-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Accepted: 12/11/2023] [Indexed: 01/05/2024]
Abstract
Parkinson's disease (PD), a neurodegenerative disorder with an unknown etiology, is primarily characterized by the degeneration of dopamine (DA) neurons. The prevalence of PD has experienced a significant surge in recent years. The unidentified etiology poses limitations to the development of effective therapeutic interventions for this condition. Helicobacter pylori (H. pylori) infection has affected approximately half of the global population. Mounting evidences suggest that H. pylori infection plays an important role in PD through various mechanisms. The autotoxin produced by H. pylori induces pro-inflammatory cytokines release, thereby facilitating the occurrence of central inflammation that leads to neuronal damage. Simultaneously, H. pylori disrupts the equilibrium of gastrointestinal microbiota with an overgrowth of bacteria in the small intestinal known as small intestinal bacterial overgrowth (SIBO). This dysbiosis of the gut flora influences the central nervous system (CNS) through microbiome-gut-brain axis. Moreover, SIBO hampers levodopa absorption and affects its therapeutic efficacy in the treatment of PD. Also, H. pylori promotes the production of defensins to regulate the permeability of the blood-brain barrier, facilitating the entry of harmful factors into the CNS. In addition, H. pylori has been found to induce gastroparesis, resulting in a prolonged transit time for levodopa to reach the small intestine. H. pylori may exploit levodopa to facilitate its own growth and proliferation, or it can inflict damage to the gastrointestinal mucosa, leading to gastrointestinal ulcers and impeding levodopa absorption. Here, this review focused on the role of H. pylori infection in PD from etiology, pathogenesis to levodopa bioavailability.
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Affiliation(s)
- Bang-Rong Wei
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Guizhou Province and Laboratory Animal Centre, Zunyi Medical University, Zunyi, Guizhou, China
| | - Yu-Jia Zhao
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Guizhou Province and Laboratory Animal Centre, Zunyi Medical University, Zunyi, Guizhou, China
| | - Yu-Feng Cheng
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Guizhou Province and Laboratory Animal Centre, Zunyi Medical University, Zunyi, Guizhou, China
| | - Chun Huang
- The Fifth People's Hospital of Chongqing, Chongqing, China
| | - Feng Zhang
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Guizhou Province and Laboratory Animal Centre, Zunyi Medical University, Zunyi, Guizhou, China.
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21
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Elkoshi Z. The Eradication of Carcinogenic Viruses in Established Solid Cancers. J Inflamm Res 2023; 16:6227-6239. [PMID: 38145011 PMCID: PMC10749098 DOI: 10.2147/jir.s430315] [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: 07/12/2023] [Accepted: 12/12/2023] [Indexed: 12/26/2023] Open
Abstract
Carcinogenic viruses (oncoviruses) can initiate cancer, but their impact on established cancer varies. Some of these viruses prolong survival while others shorten it. This study classifies oncoviruses into two categories: viruses which induce a strong CD8+T cell reaction in non-cancerous tissues, and viruses which induce a weak CD8+ T cell reaction in non-cancerous tissues. The classification proves useful in predicting the effect of oncoviruses on the prognosis of solid cancers. Therefore, while eliminating carcinogenic viruses in healthy individuals (for example by immunization) may be important for cancer prevention, this study suggests that only viruses which induce a weak CD8+ T cell reaction should be eradicated in established solid tumors. The model correctly predicts the effect of oncoviruses on survival for six out of seven known oncoviruses, indicating that immune modulation by oncoviruses has a prominent effect on prognosis. It seems that CD8+ T cell response to oncoviruses observed in infected benign tissues is retained in infected tumors. Clinical significance: the effect of oncoviruses on solid cancer prognosis can be predicted with confidence based on immunological responses when clinical data are unavailable.
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Affiliation(s)
- Zeev Elkoshi
- Research and Development Department, Taro Pharmaceutical Industries Ltd, Haifa, Israel
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22
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Wang J, Deng R, Chen S, Deng S, Hu Q, Xu B, Li J, He Z, Peng M, Lei S, Ma T, Chen Z, Zhu H, Zuo C. Helicobacter pylori CagA promotes immune evasion of gastric cancer by upregulating PD-L1 level in exosomes. iScience 2023; 26:108414. [PMID: 38047083 PMCID: PMC10692710 DOI: 10.1016/j.isci.2023.108414] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 10/01/2023] [Accepted: 11/02/2023] [Indexed: 12/05/2023] Open
Abstract
Cytotoxin-associated gene A (CagA) of Helicobacter pylori (Hp) may promote immune evasion of Hp-infected gastric cancer (GC), but potential mechanisms are still under explored. In this study, the positive rates of CagA and PD-L1 protein in tumor tissues and the high level of exosomal PD-L1 protein in plasma exosomes were significantly associated with the elevated stages of tumor node metastasis (TNM) in Hp-infected GC. Moreover, the positive rate of CagA was positively correlated with the positive rate of PD-L1 in tumor tissues and the level of PD-L1 protein in plasma exosomes, and high level of exosomal PD-L1 might indicate poor prognosis of Hp-infected GC. Mechanically, CagA increased PD-L1 level in exosomes derived from GC cells by inhibiting p53 and miRNA-34a, suppressing proliferation and anticancer effect of CD8+ T cells. This study provides sights for understanding immune evasion mediated by PD-L1. Targeting CagA and exosomal PD-L1 may improve immunotherapy efficacy of Hp-infected GC.
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Affiliation(s)
- Jinfeng Wang
- Department of Gastroduodenal and Pancreatic Surgery, Translational Medicine Joint Research Center of Liver Cancer, Laboratory of Digestive Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Clinical Research Center For Tumor of Pancreaticobiliary Duodenal Junction In Hunan Province, Changsha 410013, Hunan, China
| | - Rilin Deng
- Institute of Pathogen Biology and Immunology, College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, Hunan, China
| | - Shuai Chen
- School of Integrated Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, Hunan, China
| | - Shun Deng
- Department of Gastroduodenal and Pancreatic Surgery, Translational Medicine Joint Research Center of Liver Cancer, Laboratory of Digestive Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Clinical Research Center For Tumor of Pancreaticobiliary Duodenal Junction In Hunan Province, Changsha 410013, Hunan, China
| | - Qi Hu
- Graduates School, University of South China, Hengyang 421001, Hunan, China
| | - Biaoming Xu
- Graduates School, University of South China, Hengyang 421001, Hunan, China
| | - Junjun Li
- Department of Pathology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China
| | - Zhuo He
- Department of Gastroduodenal and Pancreatic Surgery, Translational Medicine Joint Research Center of Liver Cancer, Laboratory of Digestive Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Clinical Research Center For Tumor of Pancreaticobiliary Duodenal Junction In Hunan Province, Changsha 410013, Hunan, China
| | - Mingjing Peng
- Department of Gastroduodenal and Pancreatic Surgery, Translational Medicine Joint Research Center of Liver Cancer, Laboratory of Digestive Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Clinical Research Center For Tumor of Pancreaticobiliary Duodenal Junction In Hunan Province, Changsha 410013, Hunan, China
| | - Sanlin Lei
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Tiexiang Ma
- The Third Department of General Surgery, The Central Hospital of Xiangtan City, Xiangtan 411100, Hunan, China
| | - Zhuo Chen
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, Hunan, China
| | - Haizhen Zhu
- Institute of Pathogen Biology and Immunology, College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, Hunan, China
| | - Chaohui Zuo
- Department of Gastroduodenal and Pancreatic Surgery, Translational Medicine Joint Research Center of Liver Cancer, Laboratory of Digestive Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Clinical Research Center For Tumor of Pancreaticobiliary Duodenal Junction In Hunan Province, Changsha 410013, Hunan, China
- School of Integrated Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, Hunan, China
- Graduates School, University of South China, Hengyang 421001, Hunan, China
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23
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Hou W, Zhao Y, Zhu H. Predictive Biomarkers for Immunotherapy in Gastric Cancer: Current Status and Emerging Prospects. Int J Mol Sci 2023; 24:15321. [PMID: 37895000 PMCID: PMC10607383 DOI: 10.3390/ijms242015321] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/12/2023] [Accepted: 10/16/2023] [Indexed: 10/29/2023] Open
Abstract
Gastric cancer presents substantial management challenges, and the advent of immunotherapy has ignited renewed hope among patients. Nevertheless, a significant proportion of patients do not respond to immunotherapy, and adverse events associated with immunotherapy also occur on occasion, underscoring the imperative to identify suitable candidates for treatment. Several biomarkers, including programmed death ligand-1 expression, tumor mutation burden, mismatch repair status, Epstein-Barr Virus infection, circulating tumor DNA, and tumor-infiltrating lymphocytes, have demonstrated potential in predicting the effectiveness of immunotherapy in gastric cancer. However, the quest for the optimal predictive biomarker for gastric cancer immunotherapy remains challenging, as each biomarker carries its own limitations. Recently, multi-omics technologies have emerged as promising platforms for discovering novel biomarkers that may help in selecting gastric cancer patients likely to respond to immunotherapy. The identification of reliable predictive biomarkers for immunotherapy in gastric cancer holds the promise of enhancing patient selection and improving treatment outcomes. In this review, we aim to provide an overview of clinically established biomarkers of immunotherapy in gastric cancer. Additionally, we introduce newly reported biomarkers based on multi-omics studies in the context of gastric cancer immunotherapy, thereby contributing to the ongoing efforts to refine patient stratification and treatment strategies.
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Affiliation(s)
- Wanting Hou
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610065, China; (W.H.); (Y.Z.)
- Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610065, China
| | - Yaqin Zhao
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610065, China; (W.H.); (Y.Z.)
- Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610065, China
| | - Hong Zhu
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610065, China; (W.H.); (Y.Z.)
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Dadgar N, Edlukudige Keshava V, Raj MS, Wagner PL. The Influence of the Microbiome on Immunotherapy for Gastroesophageal Cancer. Cancers (Basel) 2023; 15:4426. [PMID: 37760397 PMCID: PMC10526145 DOI: 10.3390/cancers15184426] [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: 08/08/2023] [Revised: 08/27/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023] Open
Abstract
Immunotherapy has shown promise as a treatment option for gastroesophageal cancer, but its effectiveness is limited in many patients due to the immunosuppressive tumor microenvironment (TME) commonly found in gastrointestinal tumors. This paper explores the impact of the microbiome on the TME and immunotherapy outcomes in gastroesophageal cancer. The microbiome, comprising microorganisms within the gastrointestinal tract, as well as within malignant tissue, plays a crucial role in modulating immune responses and tumor development. Dysbiosis and reduced microbial diversity are associated with poor response rates and treatment resistance, while specific microbial profiles correlate with improved outcomes. Understanding the complex interactions between the microbiome, tumor biology, and immunotherapy is crucial for developing targeted interventions. Microbiome-based biomarkers may enable personalized treatment approaches and prediction of patient response. Interventions targeting the microbiome, such as microbiota-based therapeutics and dietary modifications, offer the potential for reshaping the gut microbiota and creating a favorable TME that enhances immunotherapy efficacy. Further research is needed to reveal the underlying mechanisms, and large-scale clinical trials will be required to validate the efficacy of microbiome-targeted interventions.
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Affiliation(s)
- Neda Dadgar
- Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44106, USA;
| | | | - Moses S. Raj
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA; (V.E.K.); (M.S.R.)
| | - Patrick L. Wagner
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA; (V.E.K.); (M.S.R.)
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Cao Y, Wang D, Mo G, Peng Y, Li Z. Gastric precancerous lesions:occurrence, development factors, and treatment. Front Oncol 2023; 13:1226652. [PMID: 37719006 PMCID: PMC10499614 DOI: 10.3389/fonc.2023.1226652] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 08/10/2023] [Indexed: 09/19/2023] Open
Abstract
Patients with gastric precancerous lesions (GPL) have a higher risk of gastric cancer (GC). However, the transformation of GPL into GC is an ongoing process that takes several years. At present, several factors including H.Pylori (Hp), flora imbalance, inflammatory factors, genetic variations, Claudin-4, gastric stem cells, solute carrier family member 26 (SLC26A9), bile reflux, exosomes, and miR-30a plays a considerable role in the transformation of GPL into GC. Moreover, timely intervention in the event of GPL can reduce the risk of GC. In clinical practice, GPL is mainly treated with endoscopy, acid suppression therapy, Hp eradication, a cyclooxygenase-2 inhibitor, aspirin, and diet. Currently, the use of traditional Chinese medicine (TCM) or combination with western medication to remove Hp and the use of TCM to treat GPL are common in Asia, particularly China, and have also demonstrated excellent clinical efficacy. This review thoroughly discussed the combining of TCM and Western therapy for the treatment of precancerous lesions as conditions allow. Consequently, this review also focuses on the causes of the development and progression of GPL, as well as its current treatment. This may help us understand GPL and related treatment.
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Affiliation(s)
- Yue Cao
- Emergency of Department, Yunnan Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Dongcai Wang
- Emergency of Department, Yunnan Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Guiyun Mo
- Emergency Teaching and Research Department of the First Clinical School of Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Yinghui Peng
- Emergency of Department, Yunnan Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Zengzheng Li
- Department of Hematology, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
- Yunnan Province Clinical Center for Hematologic Disease, The First People’s Hospital of Yunnan Province, Kunming, China
- Yunnan Blood Disease Hospital, The First People’s Hospital of Yunnan Province, Kunming, China
- National Key Clinical Specialty of Hematology, The First People’s Hospital of Yunnan Province, Kunming, China
- Yunnan Province Clinical Research Center for Hematologic Disease, The First People’s Hospital of Yunnan Province, Kunming, China
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26
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Zhu X, Li S. Nanomaterials in tumor immunotherapy: new strategies and challenges. Mol Cancer 2023; 22:94. [PMID: 37312116 PMCID: PMC10262535 DOI: 10.1186/s12943-023-01797-9] [Citation(s) in RCA: 90] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 05/31/2023] [Indexed: 06/15/2023] Open
Abstract
Tumor immunotherapy exerts its anti-tumor effects by stimulating and enhancing immune responses of the body. It has become another important modality of anti-tumor therapy with significant clinical efficacy and advantages compared to chemotherapy, radiotherapy and targeted therapy. Although various kinds of tumor immunotherapeutic drugs have emerged, the challenges faced in the delivery of these drugs, such as poor tumor permeability and low tumor cell uptake rate, had prevented their widespread application. Recently, nanomaterials had emerged as a means for treatment of different diseases due to their targeting properties, biocompatibility and functionalities. Moreover, nanomaterials possess various characteristics that overcome the defects of traditional tumor immunotherapy, such as large drug loading capacity, precise tumor targeting and easy modification, thus leading to their wide application in tumor immunotherapy. There are two main classes of novel nanoparticles mentioned in this review: organic (polymeric nanomaterials, liposomes and lipid nanoparticles) and inorganic (non-metallic nanomaterials and metallic nanomaterials). Besides, the fabrication method for nanoparticles, Nanoemulsions, was also introduced. In summary, this review article mainly discussed the research progress of tumor immunotherapy based on nanomaterials in the past few years and offers a theoretical basis for exploring novel tumor immunotherapy strategies in the future.
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Affiliation(s)
- Xudong Zhu
- Department of General Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People's Republic of China
| | - Shenglong Li
- Second Ward of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People's Republic of China.
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27
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Liu Y, Wang L, Du W, Huang Y, Guo Y, Song C, Tian Z, Niu S, Xie J, Liu J, Cheng C, Shen W. Identification of high-risk factors associated with mortality at 1-, 3-, and 5-year intervals in gastric cancer patients undergoing radical surgery and immunotherapy: an 8-year multicenter retrospective analysis. Front Cell Infect Microbiol 2023; 13:1207235. [PMID: 37325512 PMCID: PMC10264693 DOI: 10.3389/fcimb.2023.1207235] [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: 04/17/2023] [Accepted: 05/10/2023] [Indexed: 06/17/2023] Open
Abstract
Background Combining immunotherapy with surgical intervention is a prevailing and radical therapeutic strategy for individuals afflicted with gastric carcinoma; nonetheless, certain patients exhibit unfavorable prognoses even subsequent to this treatment regimen. This research endeavors to devise a machine learning algorithm to recognize risk factors with a high probability of inducing mortality among patients diagnosed with gastric cancer, both prior to and during their course of treatment. Methods Within the purview of this investigation, a cohort of 1015 individuals with gastric cancer were incorporated, and 39 variables encompassing diverse features were recorded. To construct the models, we employed three distinct machine learning algorithms, specifically extreme gradient boosting (XGBoost), random forest (RF), and k-nearest neighbor algorithm (KNN). The models were subjected to internal validation through employment of the k-fold cross-validation technique, and subsequently, an external dataset was utilized to externally validate the models. Results In comparison to other machine learning algorithms employed, the XGBoost algorithm demonstrated superior predictive capacity regarding the risk factors that affect mortality after combination therapy in gastric cancer patients for a duration of one year, three years, and five years posttreatment. The common risk factors that significantly impacted patient survival during the aforementioned time intervals were identified as advanced age, tumor invasion, tumor lymph node metastasis, tumor peripheral nerve invasion (PNI), multiple tumors, tumor size, carcinoembryonic antigen (CEA) level, carbohydrate antigen 125 (CA125) level, carbohydrate antigen 72-4 (CA72-4) level, and H. pylori infection. Conclusion The XGBoost algorithm can assist clinicians in identifying pivotal prognostic factors that are of clinical significance and can contribute toward individualized patient monitoring and management.
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Affiliation(s)
- Yuan Liu
- Department of General Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Lanyu Wang
- Department of Urology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Wenyi Du
- Department of General Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Yukang Huang
- Department of General Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Yi Guo
- Department of General Practice, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Chen Song
- Department of General Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Zhiqiang Tian
- Department of General Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Sen Niu
- Department of General Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Jiaheng Xie
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jinhui Liu
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chao Cheng
- Department of Neurosurgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Wei Shen
- Department of General Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
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28
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Noori M, Fayyaz F, Rezaei N. Impact of Helicobacter pylori infection on the efficacy of immune checkpoint inhibitors for cancer treatment: a meta-analysis. Immunotherapy 2023; 15:657-667. [PMID: 37140002 DOI: 10.2217/imt-2022-0250] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2023] Open
Abstract
Aim: The present systematic review and meta-analysis was designed to assess the impact of Helicobacter pylori infection on the efficacy of immune checkpoint inhibitors (ICIs). Materials & methods: PubMed, Scopus, Web of Science and EMBASE databases were systematically searched up to 1 February 2023. Results: Three studies comprising 263 patients treated with ICIs were included. The results of pooled analysis showed that H. pylori infection was associated with reduced overall survival and progression-free survival. Furthermore, the rate of progressive disease after administration of ICIs was higher in H. pylori-positive patients relative to H. pylori-negative patients. Conclusion: H. pylori infection status is a novel potential response biomarker for predicting the efficacy of ICIs in different cancers.
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Affiliation(s)
- Maryam Noori
- Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Urology Research Center, Tehran University of Medical Science, Tehran, Iran
| | - Farimah Fayyaz
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
- Cancer Immunology Project (CIP), Universal Scientific Education & Research Network (USERN), Tehran, Iran
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
| | - Nima Rezaei
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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29
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Dytrych P, Kejík Z, Hajduch J, Kaplánek R, Veselá K, Kučnirová K, Skaličková M, Venhauerová A, Hoskovec D, Martásek P, Jakubek M. Therapeutic potential and limitations of curcumin as antimetastatic agent. Biomed Pharmacother 2023; 163:114758. [PMID: 37141738 DOI: 10.1016/j.biopha.2023.114758] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 05/06/2023] Open
Abstract
Treatment of metastatic cancer is one of the biggest challenges in anticancer therapy. Curcumin is interesting nature polyphenolic compound with unique biological and medicinal effects, including repression of metastases. High impact studies imply that curcumin can modulate the immune system, independently target various metastatic signalling pathways, and repress migration and invasiveness of cancer cells. This review discusses the potential of curcumin as an antimetastatic agent and describes potential mechanisms of its antimetastatic activity. In addition, possible strategies (curcumin formulation, optimization of the method of administration and modification of its structure motif) to overcome its limitation such as low solubility and bioactivity are also presented. These strategies are discussed in the context of clinical trials and relevant biological studies.
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Affiliation(s)
- Petr Dytrych
- 1st Department of Surgery-Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 2, 121 08 Prague, Czech Republic
| | - Zdeněk Kejík
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic
| | - Jan Hajduch
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic
| | - Robert Kaplánek
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic
| | - Kateřina Veselá
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic
| | - Kateřina Kučnirová
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic
| | - Markéta Skaličková
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic
| | - Anna Venhauerová
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic
| | - David Hoskovec
- 1st Department of Surgery-Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 2, 121 08 Prague, Czech Republic
| | - Pavel Martásek
- Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic.
| | - Milan Jakubek
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic.
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30
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Silva-Pilipich N, Covo-Vergara Á, Smerdou C. Local Delivery of Immunomodulatory Antibodies for Gastrointestinal Tumors. Cancers (Basel) 2023; 15:cancers15082352. [PMID: 37190279 DOI: 10.3390/cancers15082352] [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: 03/17/2023] [Revised: 04/12/2023] [Accepted: 04/13/2023] [Indexed: 05/17/2023] Open
Abstract
Cancer therapy has experienced a breakthrough with the use of immune checkpoint inhibitors (ICIs) based on monoclonal antibodies (mAbs), which are able to unleash immune responses against tumors refractory to other therapies. Despite the great advancement that ICIs represent, most patients with gastrointestinal tumors have not benefited from this therapy. In addition, ICIs often induce adverse effects that are related to their systemic use. Local administration of ICIs in tumors could concentrate their effect in the malignant tissue and provide a higher safety profile. A new and attractive approach for local delivery of ICIs is the use of gene therapy vectors to express these blocking antibodies in tumor cells. Several vectors have been evaluated in preclinical models of gastrointestinal tumors to express ICIs against PD-1, PD-L1, and CTLA-4, among other immune checkpoints, with promising results. Vectors used in these settings include oncolytic viruses, self-replicating RNA vectors, and non-replicative viral and non-viral vectors. The use of viral vectors, especially when they have replication capacity, provides an additional adjuvant effect that has been shown to enhance antitumor responses. This review covers the most recent studies involving the use of gene therapy vectors to deliver ICIs to gastrointestinal tumors.
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Affiliation(s)
- Noelia Silva-Pilipich
- Division of Gene Therapy and Regulation of Gene Expression, Cima Universidad de Navarra, 31008 Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdISNA), Cancer Center Clínica Universidad de Navarra (CCUN), 31008 Pamplona, Spain
| | - Ángela Covo-Vergara
- Division of Gene Therapy and Regulation of Gene Expression, Cima Universidad de Navarra, 31008 Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdISNA), Cancer Center Clínica Universidad de Navarra (CCUN), 31008 Pamplona, Spain
| | - Cristian Smerdou
- Division of Gene Therapy and Regulation of Gene Expression, Cima Universidad de Navarra, 31008 Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdISNA), Cancer Center Clínica Universidad de Navarra (CCUN), 31008 Pamplona, Spain
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31
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Nanomaterials: Breaking through the bottleneck of tumor immunotherapy. Int J Biol Macromol 2023; 230:123159. [PMID: 36610572 DOI: 10.1016/j.ijbiomac.2023.123159] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 12/23/2022] [Accepted: 01/02/2023] [Indexed: 01/06/2023]
Abstract
Immunotherapy exerts its excellent anti-tumor effects by stimulating and enhancing the immune response of the body, and has become another important class of anti-tumor therapy besides chemotherapy, targeted therapy and radiotherapy. Various types of immunotherapeutic drugs have gained their clinical values, but the in vivo delivery of drugs still faces many challenges, such as poor tumor permeability and low tumor cell uptake rate. In recent years, owing to highly targeting properties, better biocompatibility, and easy functionalization, nanomaterials have been widely applicated in tumor treatment, especially in tumor immunotherapy. Furthermore, nanomaterials have large drug loading capacity, strong tumor targeting and easy modification, which can effectively overcome the drawbacks of traditional immunotherapy. This paper reviews the progress of nanomaterial-based tumor immunotherapy in recent years and provides a theoretical basis for exploring new nanomaterial-based tumor immunotherapy strategies.
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32
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Effect of Antacid Use on Immune Checkpoint Inhibitors in Advanced Solid Cancer Patients: A Systematic Review and Meta-analysis. J Immunother 2023; 46:43-55. [PMID: 36301729 DOI: 10.1097/cji.0000000000000442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 09/08/2022] [Indexed: 11/07/2022]
Abstract
The influence of antacids use on immune checkpoint inhibitor (ICI) efficacy remains unclear. A systematic review and meta-analysis was performed to evaluate the effect of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) on ICI efficacy in advanced solid cancer patients. A systematic literature search in PubMed, EMBASE, and Web of Science was performed to retrieve studies investigating the effect of antacid use on ICI efficacy. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and immune-related adverse events were measured using hazard ratios (HRs) or odds ratios (ORs). Thirty studies enrolling 16,147 advanced cancer patients receiving ICI treatment were included. The pooled analysis indicated that PPI use was associated with shorter OS (HR=1.40, 95% CI, 1.25-1.57) and PFS (HR=1.34, 95% CI, 1.19-1.52) in advanced cancer patients treated with ICIs. PPI use did not show effect on ORR or immune-related adverse event of advanced cancer patients receiving ICI treatment. OS, PFS, and ORR did not differ between H2RA users and non-H2RA users. In subgroup analyses, PPI use was associated with shorter OS and PFS in NSCLC and urothelial carcinoma patients and in patients treated with anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy. In addition, ICI efficacy was different in the antacid exposure time frame subgroups. In conclusion, PPI use has a negative effect on OS and PFS among advanced cancer patients receiving ICI treatment. PPIs should be cautiously administered among advanced cancer patients treated with ICI. The safety of H2RAs and the influence of H2RAs on ICI efficacy need further investigation.
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33
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Muhammad JS, Manzoor S, Cui ZG, Khoder G. DNA Methylation-Mediated Overexpression of CXCL1 in Helicobacter pylori-Induced Gastric Cancer: In Silico- and In Vitro-Based Identification of a Potential Biomarker for Carcinogenesis. Int J Mol Sci 2023; 24:795. [PMID: 36614235 PMCID: PMC9820856 DOI: 10.3390/ijms24010795] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/05/2022] [Accepted: 12/07/2022] [Indexed: 01/05/2023] Open
Abstract
Given the high global prevalence and mortality associated with gastric cancer, and its known causal link with Helicobacter pylori infection, it is important to have a biomarker to identify malignant transformation at early stages. Previously, we, and others, have reported that H. pylori-induced epigenetic changes could mediate carcinogenic transformation of the gastric cells. Also, CXCL1 secreted by gastric cancer cells was reported as a key diagnostic and prognostic biomarker for the pathogenic progression of gastric cancer. In this study, for the first time, we aimed to investigate the role of H. pylori-induced DNA methylation-based epigenetic regulation of CXCL1. In silico analysis of publicly available datasets and in vitro experiments were performed. Our results showed that CXCL1 is highly expressed in both gastric cancer tissues and gastric cancer cells infected with H. pylori. Further, we showed and confirmed that H. pylori-mediated overexpression of CXCL1 is due to hypomethylation of its promoter region. Since epigenetic events such as DNA methylation happen early in the sequence; H. pylori-induced CXCL1 hypomethylation could likely be detected at an early stage of gastric cancer development. Epigenetic modifications, such as CXCL1 hypomethylation, are reversible and could potentially be a therapeutic target using demethylation drugs.
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Affiliation(s)
- Jibran Sualeh Muhammad
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Shaista Manzoor
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Zheng-Guo Cui
- Department of Environmental Health, University of Fukui School of Medical Sciences, Fukui 910-1193, Japan
| | - Ghalia Khoder
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates
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34
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Liang M, Wang X, Cai D, Guan W, Shen X. Tissue-resident memory T cells in gastrointestinal tumors: turning immune desert into immune oasis. Front Immunol 2023; 14:1119383. [PMID: 36969190 PMCID: PMC10033836 DOI: 10.3389/fimmu.2023.1119383] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/27/2023] [Indexed: 03/29/2023] Open
Abstract
Tissue-resident memory T cells (Trm) are a particular type of T cell subgroup, which stably reside in tissues and have been revealed to be the most abundant memory T cell population in various tissues. They can be activated in the local microenvironment by infection or tumor cells and rapidly clean them up to restore homeostasis of local immunity in gastrointestinal tissues. Emerging evidence has shown that tissue-resident memory T cells have great potential to be mucosal guardians against gastrointestinal tumors. Therefore, they are considered potential immune markers for immunotherapy of gastrointestinal tumors and potential extraction objects for cell therapy with essential prospects in clinical translational therapy. This paper systematically reviews the role of tissue-resident memory T cells in gastrointestinal tumors and looks to the future of their prospect in immunotherapy to provide a reference for clinical application.
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35
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Moehler M, Högner A, Wagner AD, Obermannova R, Alsina M, Thuss-Patience P, van Laarhoven H, Smyth E. Recent progress and current challenges of immunotherapy in advanced/metastatic esophagogastric adenocarcinoma. Eur J Cancer 2022; 176:13-29. [PMID: 36183651 DOI: 10.1016/j.ejca.2022.08.023] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 08/12/2022] [Accepted: 08/22/2022] [Indexed: 12/15/2022]
Abstract
The new era of immunotherapy is successfully implemented in the treatment of metastatic/locally advanced esophagogastric adenocarcinoma (EGAC), as it has been investigated in combinations with/without chemotherapy in human epidermal growth factor receptor 2 (Her2)-positive and Her2-negative tumors. Recent approvals of immune checkpoint inhibitors (ICI) enrich the therapeutic landscape in nearly every therapeutic line. Based on CHECKMATE-649, the combination of nivolumab and chemotherapy in first-line therapy of programmed cell death protein 1 (PD-L1)-positive patients with advanced gastroesophageal junction cancer (GEJC), esophageal cancer (EC), and gastric cancer (GC) was approved in Europe for PD-L1 combined positivity score (CPS) ≥ 5 patients and independently from PD-L1 score in the USA and Asia. Based on KEYNOTE-590, patients with advanced GEJC and EC qualify for the combination of pembrolizumab plus chemotherapy in Europe (CPS ≥ 10) and the USA. For Her2-positive patients, trastuzumab with first-line chemotherapy plus pembrolizumab has beneficial response rates and resulted in approval in the USA (KEYNOTE-811). In third-line therapy, superior overall survival (OS) was achieved by the administration of nivolumab (approval in Japan, ATTRACTION-02), and pembrolizumab shows a positive effect on the duration of response (KEYNOTE-059). Questions of resistance to immunotherapy or the role of gender in response to ICI need to be clarified. This review provides an overview of the current approvals of ICI in advanced EGAC and reflects results of relevant phase II/III trials with focus on possible biomarkers, including PD-L1 CPS and microsatellite-instability (MSI) status.
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Affiliation(s)
- Markus Moehler
- Universitätsmedizin Mainz, Johannes Gutenberg Universität Mainz, 55131 Mainz, Germany.
| | - Anica Högner
- Charité - University Medicine Berlin, Department of Haematology, Oncology and Cancer Immunology, Campus Virchow-Klinikum, Berlin, Germany
| | - Anna D Wagner
- Department of Oncology, Division of Medical Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Radka Obermannova
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Maria Alsina
- Vall D'Hebron University Hospital, Department of Medical Oncology, and Vall D'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Passeig de La Vall D'Hebron, Barcelona, Spain
| | - Peter Thuss-Patience
- Charité - University Medicine Berlin, Department of Haematology, Oncology and Cancer Immunology, Campus Virchow-Klinikum, Berlin, Germany
| | - Hanneke van Laarhoven
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Elizabeth Smyth
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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