[摘 要] 尽管基于T细胞的免疫检查点阻断（ICB）和过继性T细胞治疗已在临床上取得了显著疗效，但大多数实体瘤患者仍无 法实现对免疫疗法的长期应答。其中一个重要原因是肿瘤微环境（TME）中复杂的代谢模式和抑制性信号会引发免疫细胞的代 谢重编程，从而削弱其抗肿瘤效应。本文回顾不同分化状态的CD8+ T细胞的代谢偏好性，探讨CD8+ T细胞在与肿瘤细胞和TME 相互作用过程中发生的代谢变化，讨论这些代谢变化如何影响CD8+ T细胞分化、功能和干性，以及如何利用代谢分子或者代谢通 路来增强CD8+ T细胞的抗肿瘤能力，从而实现嵌合抗原受体基因修饰T淋巴细胞（CAR-T细胞）疗法和ICB疗法增效。

[Abstract] Despite the remarkable clinical efficacy achieved by immune checkpoint blockade (ICB) and adoptive T cell therapy, the majority of patients with solid tumors still fail to achieve long-term responses to immunotherapy. One important reason is the complex metabolic patterns and inhibitory signals within the tumor microenvironment (TME), which induce metabolic reprogramming in immune cells and thereby impair their anti-tumor efficacy. This review summarizes the metabolic preferences of CD8+ T cells across various differentiation states, explores the metabolic changes that occur during their interaction with tumor cells and the TME, and discusses how these metabolic changes affect differentiation, function, and stemness of CD8+ T cells. Additionally, strategies that target metabolic molecules or pathways are highlighted to enhance the antitumor ability of CD8+ T cells, thereby improving the efficacy of chimeric antigen receptor gene-modified T lymphocyte (CAR-T cell) immunotherapy and ICB therapy.

[基金项目] 癌症、心脑血管、呼吸和代谢性疾病防治研究国家科技重大专项（No. 2024ZD0519900）；国家自然科学基金 （No. 82230056，No. 82471870）；国家生物药技术创新中心“揭榜挂帅”技术攻关项目（No. NCTIB2023XB02006）