• Xiaoli Pan, Jiajia Wang, Lianjun Zhang, Guideng Li, and 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.
• Chin. Med. J. 2024 Apr 5; 137 (7): 762775762-775.

AbstractThe 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 differentiation. 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.Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

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