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Immunometabolism:a new dimension in immunotherapy resistance

frontiers of Medicine 2023年第4期17卷 585-616页

作者： Chaoyue Xiao Wei Xiong Yiting Xu Ji’an Zou Yue Zeng Junqi Liu Yurong Peng Chunhong Hu fang wu Department of Oncology The Second Xiangya HospitalCentral South UniversityChangsha 410011China NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Cancer Research InstituteCentral South UniversityChangsha 410078China Xiangya School of Medicine Central South UniversityChangsha 410013China Hunan Cancer Mega-Data Intelligent Application and Engineering research Centre Changsha 410011China Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer The Second Xiangya HospitalCentral South UniversityChangsha 410011China Hunan Key Laboratory of Tumor Models and Individualized Medicine The Second Xiangya HospitalCentral South UniversityChangsha 410011China

Immune checkpoint inhibitors(ICIs)have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment,while substantial patients remain unresponsive or develop resistance to ICIs as a single agent,which is traceable to cellular metabolic *** dysregulated metabolism has long been adjudged as a hallmark of tumor,it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of ***,people used to pay more attention to the effect of tumor cell metabolism on immunocytes,but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation,which opens up a whole new frontier called *** metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy,whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune ***,we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes,and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.

关键词： immune cell immunometabolism metabolic reprogramming immunotherapy resistance tumor microenvironment immune checkpoint inhibitor

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