The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T cells.Upon antigen exposure,T cells undergo metabolic reprogramming,leading to the development of functional effectors or memory populations.However,within the tumor microenvironment(TME),metabolic stress impairs CD8+T cell anti-tumor immunity,resulting in exhausted dif-ferentiation.Recent studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell immunotherapy.In this review,we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory conditions.Furthermore,we delved into the different metabolic switches that occur during T cell exhaustion,exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion,ultimately leading to a persistently exhausted state.Understanding the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.
Xiaoli Pan;Jiajia Wang;Lianjun Zhang;Guideng Li;Bo Huang
National Key Laboratory of Immunity and Inflammation,Suzhou Institute of Systems Medicine,Chinese Academy of Medical Sciences & Peking Union Medical College,Suzhou,Jiangsu 215123,China||Key Laboratory of Synthetic Biology Regulatory Element,Suzhou Institute of Systems Medicine,Chinese Academy of Medical Sciences & Peking Union Medical College,Suzhou,Jiangsu 215123,ChinaDepartment of Immunology & National Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences(CAMS)& Peking Union Medical College,Beijing 100005,China||Department of Biochemistry & Molecular Biology,Tongji Medical College,Huazhong University of Science & Technology,Wuhan,Hubei 430030,China
T cell immunotherapy;T cell differentiation;T cell exhaustion;Metabolic reprogramming;Tumor microenvironment
《中华医学杂志（英文版）》 2024 (007)
762-775 / 14
This work was supported by grants from the National Natural Science Foundation of China(Nos.81788101,82271775,and 81972875),the Chinese Academy of Med-ical Sciences Innovation Fund for Medical Sciences(Nos.2021-I2M-1-021,2021-I2M-1-061,and 2022-I2M-1-047),the Haihe Laboratory of Cell Ecosystem Innovation Fund(No.22HHXBSS00009),and the Natural Science Foundation Outstanding Youth Fund of Jiangsu Province(Nos.BK20220049 and BK20211505).
10.1097/CM9.0000000000002989
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