{"title":"癌症免疫疗法中 M2 肿瘤相关巨噬细胞 (TAM) 的极化。","authors":"Indy Bui, Benjamin Bonavida","doi":"10.1615/CritRevOncog.2024053830","DOIUrl":null,"url":null,"abstract":"<p><p>We have witnessed in the last decade new milestones in the treatment of various resistant cancers with new immunotherapeutic modalities. These advances have resulted in significant objective durable clinical responses in a subset of cancer patients. These findings strongly suggested that immunotherapy should be considered for the treatment of all subsets of cancer patients. Accordingly, the mechanisms underlying resistance to immunotherapy must be explored and develop new means to target these resistant factors. One of the pivotal resistance mechanisms in the tumor microenvironment (TME) is the high infiltration of tumor-associated macrophages (TAMs) that are highly immunosuppressive and responsible, in large part, of cancer immune evasion. Thus, various approaches have been investigated to target the TAMs to restore the anti-tumor immune response. One approach is to polarize the M2 TAMS to the M1 phenotype that participates in the activation of the anti-tumor response. In this review, we discuss the various and differential properties of the M1 and M2 phenotypes, the molecular signaling pathways that participate in the polarization, and various approaches used to target the polarization of the M2 TAMs into the M1 anti-tumor phenotype. These approaches include inhibitors of histone deacetylases, PI3K inhibitors, STAT3 inhibitors, TLR agonists, and metabolic reprogramming. Clearly, due to the distinct features of various cancers and their heterogeneities, a single approach outlined above might only be effective against some cancers and not others. In addition, targeting by itself may not be efficacious unless used in combination with other therapeutic modalities.</p>","PeriodicalId":35617,"journal":{"name":"Critical Reviews in Oncogenesis","volume":"29 4","pages":"75-95"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Polarization of M2 Tumor-Associated Macrophages (TAMs) in Cancer Immunotherapy.\",\"authors\":\"Indy Bui, Benjamin Bonavida\",\"doi\":\"10.1615/CritRevOncog.2024053830\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>We have witnessed in the last decade new milestones in the treatment of various resistant cancers with new immunotherapeutic modalities. These advances have resulted in significant objective durable clinical responses in a subset of cancer patients. These findings strongly suggested that immunotherapy should be considered for the treatment of all subsets of cancer patients. Accordingly, the mechanisms underlying resistance to immunotherapy must be explored and develop new means to target these resistant factors. One of the pivotal resistance mechanisms in the tumor microenvironment (TME) is the high infiltration of tumor-associated macrophages (TAMs) that are highly immunosuppressive and responsible, in large part, of cancer immune evasion. Thus, various approaches have been investigated to target the TAMs to restore the anti-tumor immune response. One approach is to polarize the M2 TAMS to the M1 phenotype that participates in the activation of the anti-tumor response. In this review, we discuss the various and differential properties of the M1 and M2 phenotypes, the molecular signaling pathways that participate in the polarization, and various approaches used to target the polarization of the M2 TAMs into the M1 anti-tumor phenotype. These approaches include inhibitors of histone deacetylases, PI3K inhibitors, STAT3 inhibitors, TLR agonists, and metabolic reprogramming. Clearly, due to the distinct features of various cancers and their heterogeneities, a single approach outlined above might only be effective against some cancers and not others. In addition, targeting by itself may not be efficacious unless used in combination with other therapeutic modalities.</p>\",\"PeriodicalId\":35617,\"journal\":{\"name\":\"Critical Reviews in Oncogenesis\",\"volume\":\"29 4\",\"pages\":\"75-95\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Reviews in Oncogenesis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1615/CritRevOncog.2024053830\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Oncogenesis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1615/CritRevOncog.2024053830","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Polarization of M2 Tumor-Associated Macrophages (TAMs) in Cancer Immunotherapy.
We have witnessed in the last decade new milestones in the treatment of various resistant cancers with new immunotherapeutic modalities. These advances have resulted in significant objective durable clinical responses in a subset of cancer patients. These findings strongly suggested that immunotherapy should be considered for the treatment of all subsets of cancer patients. Accordingly, the mechanisms underlying resistance to immunotherapy must be explored and develop new means to target these resistant factors. One of the pivotal resistance mechanisms in the tumor microenvironment (TME) is the high infiltration of tumor-associated macrophages (TAMs) that are highly immunosuppressive and responsible, in large part, of cancer immune evasion. Thus, various approaches have been investigated to target the TAMs to restore the anti-tumor immune response. One approach is to polarize the M2 TAMS to the M1 phenotype that participates in the activation of the anti-tumor response. In this review, we discuss the various and differential properties of the M1 and M2 phenotypes, the molecular signaling pathways that participate in the polarization, and various approaches used to target the polarization of the M2 TAMs into the M1 anti-tumor phenotype. These approaches include inhibitors of histone deacetylases, PI3K inhibitors, STAT3 inhibitors, TLR agonists, and metabolic reprogramming. Clearly, due to the distinct features of various cancers and their heterogeneities, a single approach outlined above might only be effective against some cancers and not others. In addition, targeting by itself may not be efficacious unless used in combination with other therapeutic modalities.
期刊介绍:
The journal is dedicated to extensive reviews, minireviews, and special theme issues on topics of current interest in basic and patient-oriented cancer research. The study of systems biology of cancer with its potential for molecular level diagnostics and treatment implies competence across the sciences and an increasing necessity for cancer researchers to understand both the technology and medicine. The journal allows readers to adapt a better understanding of various fields of molecular oncology. We welcome articles on basic biological mechanisms relevant to cancer such as DNA repair, cell cycle, apoptosis, angiogenesis, tumor immunology, etc.