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肿瘤免疫治疗的新视角:T细胞代谢调控OA北大核心

A new perspective on tumor immunotherapy:metabolic regulation of T cells

中文摘要英文摘要

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.

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.

李华域;李春阳;马春红

山东大学基础医学院 实验畸形学教育部重点实验室,山东 济南 250012山东大学基础医学院 实验畸形学教育部重点实验室,山东 济南 250012山东大学基础医学院 实验畸形学教育部重点实验室,山东 济南 250012

医药卫生

CD8+T细胞代谢重编程肿瘤微环境CAR-T细胞

CD8+T cellmetabolic reprogrammingtumor microenvironment(TME)chimeric antigen receptor gene-modified T lymphocyte(CAR-T cell)

《中国肿瘤生物治疗杂志》 2025 (7)

673-680,8

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)

10.3872/j.issn.1007-385x.2025.07.001

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