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Yi SY, Wei MZ, Zhao L. Targeted immunotherapy to cancer stem cells: A novel strategy of anticancer immunotherapy. Crit Rev Oncol Hematol 2024; 196:104313. [PMID: 38428702 DOI: 10.1016/j.critrevonc.2024.104313] [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: 10/14/2023] [Revised: 02/04/2024] [Accepted: 02/26/2024] [Indexed: 03/03/2024] Open
Abstract
Cancer is a major disease that endangers human health. Cancer drug resistance and relapse are the two main causes contributing to cancer treatment failure. Cancer stem cells (CSCs) are a small fraction of tumor cells that are responsible for tumorigenesis, metastasis, relapse, and resistance to conventional anticancer therapies. Therefore, CSCs are considered to be the root of cancer recurrence, metastasis, and drug resistance. Novel anticancer strategies need to face this new challenge and explore their efficacy against CSCs. Recently, immunotherapy has made rapid advances in cancer treatment, and its potential against CSCs is also an interesting area of research. Meanwhile, immunotherapy strategies are novel therapeutic modalities with promising results in targeting CSCs. In this review, we summarize the targeting of CSCs by various immunotherapy strategies such as monoclonal antibodies(mAb), tumor vaccines, immune checkpoint inhibitors, and chimeric antigen receptor-T cells(CAR-T) in pre-clinical and clinical studies. This review provides new insights into the application of these immunotherapeutic approaches to potential anti-tumor therapies in the future.
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Affiliation(s)
- Shan-Yong Yi
- Department of Oncology of the Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zheng Zhou, Henan Province 450007, China.
| | - Mei-Zhuo Wei
- Department of Oncology of the Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zheng Zhou, Henan Province 450007, China
| | - Ling Zhao
- Department of Oncology of the Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zheng Zhou, Henan Province 450007, China.
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Chen M, Xiao S, Sun P, Li Y, Xu Z, Wang J. Morusin suppresses the stemness characteristics of gastric cancer cells induced by hypoxic microenvironment through inhibition of HIF-1α accumulation. Toxicon 2024; 241:107675. [PMID: 38432611 DOI: 10.1016/j.toxicon.2024.107675] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 02/26/2024] [Accepted: 02/29/2024] [Indexed: 03/05/2024]
Abstract
Gastric cancer (GC) is a common, life-threatening malignancy that contributes to the global burden of cancer-related mortality, as conventional therapeutic modalities show limited effects on GC. Hence, it is critical to develop novel agents for GC therapy. Morusin, a typical prenylated flavonoid, possesses antitumor effects against various cancers. The present study aimed to demonstrate the inhibitory effect and mechanism of morusin on the stemness characteristics of human GC in vitro under hypoxia and to explore the potential molecular mechanisms. The effects of morusin on cell proliferation and cancer stem cell-like properties of the human GC cell lines SNU-1 and AGS were assessed by MTT assay, colony formation test, qRT-PCR, flow cytometry analysis, and sphere formation test under hypoxia or normoxia condition through in vitro assays. The potential molecular mechanisms underlying the effects of morusin on the stem-cell-like properties of human GC cells in vitro were investigated by qRT-PCR, western blotting assay, and immunofluorescence assay by evaluating the nuclear translocation and expression level of hypoxia-inducible factor-1α (HIF-1α). The results showed that morusin exerted growth inhibitory effects on SNU-1 and AGS cells under hypoxia in vitro. Moreover, the proportions of CD44+/CD24- cells and the sphere formation ability of SNU-1 and AGS reduced in a dose-dependent manner following morusin treatment. The expression levels of stem cell-related genes, namely Nanog, OCT4, SOX2, and HIF-1α, gradually decreased, and the nuclear translocation of the HIF-1α protein was apparently attenuated. HIF-1α overexpression partially reversed the abovementioned effects of morusin. Taken together, morusin could restrain stemness characteristics of GC cells by inhibiting HIF-1α accumulation and nuclear translocation and could serve as a promising compound for GC treatment.
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Affiliation(s)
- Mo Chen
- Department of Gastrointestinal and Burn Plastic Surgery, Pu'er People's Hospital, Pu 'er 665000, Yunnan Province, China.
| | - Shufeng Xiao
- Department of Gastrointestinal and Burn Plastic Surgery, Pu'er People's Hospital, Pu 'er 665000, Yunnan Province, China.
| | - Ping Sun
- Department of Science and Education, Pu'er People's Hospital, Pu 'er 665000, Yunnan Province, China.
| | - Yongfu Li
- Department of Science and Education, Pu'er People's Hospital, Pu 'er 665000, Yunnan Province, China.
| | - Zhixing Xu
- Department of Neuro surgery, Pu'er People's Hospital, Pu 'er 665000, Yunnan Province, China.
| | - Jun Wang
- Department of Medical Laboratory Center, Pu'er People's Hospital, Pu 'er 665000, Yunnan Province, China.
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Yu F, Zhang Z, Chang X, Ye X, Cheng H, Li Y, Cui H. Immunization with Embryonic Stem Cells/Induced Pluripotent Stem Cells Induces Effective Immunity against Ovarian Tumor-Initiating Cells in Mice. Stem Cells Int 2023; 2023:8188324. [PMID: 38058983 PMCID: PMC10696476 DOI: 10.1155/2023/8188324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 09/07/2023] [Accepted: 10/10/2023] [Indexed: 12/08/2023] Open
Abstract
Cancer stem cells (CSCs) express pluripotent markers and share many features with normal pluripotent stem cells. It is possible that immunity induced by embryonic stem cells (ESCs) and induced pluripotent stem cells- (IPSCs-) based vaccines may selectively target CSCs. In our study, cells expressing the pluripotent marker CD133 in the murine ovarian cancer cell-line ID8 were isolated and identified as CSCs. We investigated the preventive efficacy of ESCs and IPSCs-based vaccines against the development of ovarian cancer in vivo and evaluated the humoral and cellular immunities targeting CSCs in vitro. Our study showed that preimmunization with both mouse-derived embryonic stem cells (mESCs) and mouse-induced pluripotent stem cells (mIPSCs) lysates, combined with an immunostimulatory adjuvant CpG, elicited strong humoral and cellular responses. These responses effectively suppressed the development of CSC-derived tumors. Immune sera collected from mESCs and mIPSCs-vaccinated mice contained antibodies that were capable of selectively targeting CSCs, resulting in the lysis of CSCs in the presence of complement. Cytotoxic T-lymphocytes generated from splenocytes of mESCs and mIPSCs-vaccinated hosts could secrete interferon- (IFN-) γ in response to CSCs and kill CSCs in vitro. These findings indicate that vaccines based on mESCs and mIPSCs can elicit effective antitumor immunities. These immunities are related to the conferring of humoral and cellular responses that directly target CSCs.
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Affiliation(s)
- Fengsheng Yu
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing 100044, China
- Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
| | - Zujuan Zhang
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing 100044, China
- Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China
| | - Xiaohong Chang
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing 100044, China
| | - Xue Ye
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing 100044, China
| | - Hongyan Cheng
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing 100044, China
| | - Yi Li
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing 100044, China
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China
| | - Heng Cui
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing 100044, China
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China
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Geng S, Fu Y, Fu S, Wu K. A tumor microenvironment-related risk model for predicting the prognosis and tumor immunity of breast cancer patients. Front Immunol 2022; 13:927565. [PMID: 36059555 PMCID: PMC9433750 DOI: 10.3389/fimmu.2022.927565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
Background This study aimed to construct a tumor microenvironment (TME)-related risk model to predict the overall survival (OS) of patients with breast cancer. Methods Gene expression data from The Cancer Genome Atlas was used as the training set. Differentially expressed gene analysis, prognosis analysis, weighted gene co-expression network analysis, Least Absolute Shrinkage and Selection Operator regression analysis, and Wald stepwise Cox regression were performed to screen for the TME-related risk model. Three Gene Expression Omnibus databases were used to validate the predictive efficiency of the prognostic model. The TME-risk-related biological function was investigated using the gene set enrichment analysis (GSEA) method. Tumor immune and mutation signatures were analyzed between low- and high-TME-risk groups. The patients’ response to chemotherapy and immunotherapy were evaluated by the tumor immune dysfunction and exclusion (TIDE) score and immunophenscore (IPS). Results Five TME-related genes were screened for constructing a prognostic signature. Higher TME risk scores were significantly associated with worse clinical outcomes in the training set and the validation set. Correlation and stratification analyses also confirmed the predictive efficiency of the TME risk model in different subtypes and stages of breast cancer. Furthermore, immune checkpoint expression and immune cell infiltration were found to be upregulated in the low-TME-risk group. Biological processes related to immune response functions were proved to be enriched in the low-TME-risk group through GSEA analysis. Tumor mutation analysis and TIDE and IPS analyses showed that the high-TME-risk group had more tumor mutation burden and responded better to immunotherapy. Conclusion The novel and robust TME-related risk model had a strong implication for breast cancer patients in OS, immune response, and therapeutic efficiency.
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The Protective Role of 4-Acetylarylquinolinol B in Different Pathological Processes. Curr Issues Mol Biol 2022; 44:2362-2373. [PMID: 35678690 PMCID: PMC9164036 DOI: 10.3390/cimb44050161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 05/15/2022] [Accepted: 05/20/2022] [Indexed: 12/01/2022] Open
Abstract
Antrodia cinnamomea is a traditional plant and a unique fungus native to Taiwan that has been reported to have many biological functions, including anti-inflammatory and anticancer activities. The compound 4-acetylarylquinolinol B (4-AAQB) is one of the main bioactive compounds in the stamens of Antrodia cinnamomea, and has many biological functions, such as anti-inflammatory, antiproliferative, blood sugar reduction, antimetastasis, and vascular tone relaxation. In recent years, the increasing evidences have shown that 4-AAQB is involved in many diseases; however, the relevant mechanisms have not been fully clarified. This review aimed to clarify the improvement by 4-AAQB in different pathological processes, as well as the compound’s molecular mechanisms, in order to provide a theoretical reference for future related research
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Zhang Q, Li W. Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy. World J Stem Cells 2022; 14:267-286. [PMID: 35662861 PMCID: PMC9136564 DOI: 10.4252/wjsc.v14.i4.267] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/19/2022] [Accepted: 04/25/2022] [Indexed: 02/06/2023] Open
Abstract
Cancer stem cells (CSCs) possess self-renewal and differentiation potential, which may be related to recurrence, metastasis, and radiochemotherapy resistance during tumor treatment. Understanding the mechanisms via which CSCs maintain self-renewal may reveal new therapeutic targets for attenuating CSC resistance and extending patient life-span. Recent studies have shown that amino acid metabolism plays an important role in maintaining the self-renewal of CSCs and is involved in regulating their tumorigenicity characteristics. This review summarizes the relationship between CSCs and amino acid metabolism, and discusses the possible mechanisms by which amino acid metabolism regulates CSC characteristics particularly self-renewal, survival and stemness. The ultimate goal is to identify new targets and research directions for elimination of CSCs.
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Affiliation(s)
- Qi Zhang
- Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Wei Li
- Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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Mehraj U, Ganai RA, Macha MA, Hamid A, Zargar MA, Bhat AA, Nasser MW, Haris M, Batra SK, Alshehri B, Al-Baradie RS, Mir MA, Wani NA. The tumor microenvironment as driver of stemness and therapeutic resistance in breast cancer: New challenges and therapeutic opportunities. Cell Oncol (Dordr) 2021; 44:1209-1229. [PMID: 34528143 DOI: 10.1007/s13402-021-00634-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2021] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Breast cancer (BC), the second most common cause of cancer-related deaths, remains a significant threat to the health and wellness of women worldwide. The tumor microenvironment (TME), comprising cellular components, such as cancer-associated fibroblasts (CAFs), immune cells, endothelial cells and adipocytes, and noncellular components such as extracellular matrix (ECM), has been recognized as a critical contributor to the development and progression of BC. The interplay between TME components and cancer cells promotes phenotypic heterogeneity, cell plasticity and cancer cell stemness that impart tumor dormancy, enhanced invasion and metastasis, and the development of therapeutic resistance. While most previous studies have focused on targeting cancer cells with a dismal prognosis, novel therapies targeting stromal components are currently being evaluated in preclinical and clinical studies, and are already showing improved efficacies. As such, they may offer better means to eliminate the disease effectively. CONCLUSIONS In this review, we focus on the evolving concept of the TME as a key player regulating tumor growth, metastasis, stemness, and the development of therapeutic resistance. Despite significant advances over the last decade, several clinical trials focusing on the TME have failed to demonstrate promising effectiveness in cancer patients. To expedite clinical efficacy of TME-directed therapies, a deeper understanding of the TME is of utmost importance. Secondly, the efficacy of TME-directed therapies when used alone or in combination with chemo- or radiotherapy, and the tumor stage needs to be studied. Likewise, identifying molecular signatures and biomarkers indicating the type of TME will help in determining precise TME-directed therapies.
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Affiliation(s)
- Umar Mehraj
- Department of Bioresources, University of Kashmir, Srinagar, Jammu & Kashmir, India
| | - Rais A Ganai
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science & Technology , Awantipora, Jammu & Kashmir, India
| | - Muzafar A Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science & Technology , Awantipora, Jammu & Kashmir, India
| | - Abid Hamid
- Department of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal, J&K, India
| | - Mohammed A Zargar
- Department of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal, J&K, India
| | - Ajaz A Bhat
- Translational Medicine, Research Branch, Sidra Medicine, Doha, Qatar
| | - Mohd Wasim Nasser
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Mohammad Haris
- Translational Medicine, Research Branch, Sidra Medicine, Doha, Qatar.,Laboratory of Animal Research, Qatar University, Doha, Qatar
| | - Surinder K Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.,Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Lincoln, NE, USA.,Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - Bader Alshehri
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Almajmaah, Kingdom of Saudi Arabia
| | - Raid Saleem Al-Baradie
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Almajmaah, Kingdom of Saudi Arabia
| | - Manzoor A Mir
- Department of Bioresources, University of Kashmir, Srinagar, Jammu & Kashmir, India.
| | - Nissar Ahmad Wani
- Department of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal, J&K, India.
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Yin Q, Shi X, Lan S, Jin H, Wu D. Effect of melanoma stem cells on melanoma metastasis. Oncol Lett 2021; 22:566. [PMID: 34113394 PMCID: PMC8185701 DOI: 10.3892/ol.2021.12827] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/07/2021] [Indexed: 12/24/2022] Open
Abstract
Cancer stem cells (CSCs) are involved in the metastatic process, the resistance of many types of cancer to therapeutic treatments and consequently the onset of recurrences. The CSC concept therefore significantly extends our understanding of melanoma biology. More recently, melanoma stem cells (MSCs) have been described in melanoma as expressing specific biomarkers. These primitive melanoma cells are not only capable of self-renewal and differentiation plasticity, but may also confer virulence via immune evasion and multidrug resistance, and potentially, via vasculogenic mimicry and transition to migratory and metastasizing derivatives. This review will present the specific biomarkers of MSCs, including CD133, ATP binding cassette subfamily B member 5, CD271, CD20 and aldehyde dehydrogenase, which can regulate the transduction of tumor-related signals. These signal molecules can reversely act on tumor cells and regulate tumor angiogenesis, leading to the occurrence of melanoma metastasis. Targeting these specific biomarkers could inhibit the progression of melanoma and may help the development of novel therapeutic strategies for melanoma.
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Affiliation(s)
- Qiliang Yin
- Department of Tumor Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Xiumin Shi
- Department of Tumor Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Shijie Lan
- Department of Tumor Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Haofan Jin
- Department of Tumor Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Di Wu
- Department of Tumor Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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