← 返回前沿论文

过去十年肿瘤中 CAR-T 细胞耗竭:线粒体代谢作为对抗靶点

英文原题:CAR-T Cell Exhaustion in Cancer over the Past Decade: Mitochondrial Metabolism as a Target for Counteraction.

查看英文原题

CAR-T Cell Exhaustion in Cancer over the Past Decade: Mitochondrial Metabolism as a Target for Counteraction.

PubMed 2026/01/02(内容时间) Cancer Lett Q1 · IF 11.8(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

CAR-T(CAR-T)细胞疗法是癌症免疫治疗的重要进展,但仍面临多项挑战,其中T细胞耗竭是限制免疫治疗成功的关键障碍。靶向线粒体代谢有望缓解耗竭并增强CAR-T 细胞持久性。从机制上看,肿瘤微环境中的线粒体功能障碍会扰乱能量代谢、活性氧(ROS)稳态和细胞存活,损害CAR-T 功能。本文综述CAR-T 疗法用于癌症时面临的临床挑战,并总结以线粒体为中心、通过优化代谢通路克服部分障碍的方法。文章强调线粒体代谢在增强CAR-T 疗效和持久性方面的重要作用。未来突破将依赖有力临床证据和精准代谢调控,以提升CAR-T 疗法。

展开英文摘要原文

Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a transformative advancement in cancer immunotherapy, but remains limited by multiple challenges. The exhaustion of T cells represents a critical obstacle limiting the success of immunotherapeutic interventions. Targeting mitochondrial metabolism offers a promising approach to mitigate exhaustion and enhance CAR-T persistence.

Mechanistically, mitochondrial dysfunction within the tumor microenvironment disrupts energy metabolism, reactive oxygen species (ROS) homeostasis, and cell survival, impairing CAR-T function.

Here, we review the current challenges facing the clinical application of CAR-T therapy in cancers and summarize mitochondrial-centered approaches to overcome some of these obstacles by optimizing mitochondrial metabolic pathways.

We emphasize the essential role of mitochondrial metabolism in augmenting therapeutic efficacy and persistence of CAR-T cells. Future breakthroughs will depend on robust clinical evidence and precise metabolic modulation to enhance CAR-T therapies.

论文信息

作者
Si L、Wei D、Pan J、Baleeiro RB、Chard Dunmall LS、Wang Y
第一作者单位
State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, School of Convergence Medicine, Zhengzhou University, Zhengzhou, 450052, China.China
通讯作者单位
Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK. Electronic address: yaohe.wang@qmul.ac.uk.United Kingdom
文献类型
综述
期刊
Cancer letters2026 Feb 28
原文标识
PubMed 41485684 · DOI 10.1016/j.canlet.2026.218240