Immunometabolism:a new dimension in immunotherapy resistance  

作　　者：Chaoyue Xiao Wei Xiong Yiting Xu Ji’an Zou Yue Zeng Junqi Liu Yurong Peng Chunhong Hu Fang Wu 

机构地区：[1]Department of Oncology,The Second Xiangya Hospital,Central South University,Changsha 410011,China [2]NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education,Cancer Research Institute,Central South University,Changsha 410078,China [3]Xiangya School of Medicine,Central South University,Changsha 410013,China [4]Hunan Cancer Mega-Data Intelligent Application and Engineering Research Centre,Changsha 410011,China [5]Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer,The Second Xiangya Hospital,Central South University,Changsha 410011,China [6]Hunan Key Laboratory of Tumor Models and Individualized Medicine,The Second Xiangya Hospital,Central South University,Changsha 410011,China

出　　处：《Frontiers of Medicine》2023年第4期585-616,共32页医学前沿（英文版）

基　　金：supported by research grants from the National Natural Science Foundation of China(No.82272806);the Natural Science Foundation of Hunan Province for Excellent Young Scholars(No.2021JJ20088);Frontier Cross Research Project of Central South University(2023QYJC039)to Fang Wu.

摘　　要：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 dysfunction.Although 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 immunocytes.Correspondingly,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 immunometabolism.The 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 response.Herein,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 

分 类 号：R730.51[医药卫生—肿瘤]