决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
英文原题:CAR-T Cell Exhaustion in Cancer over the Past Decade: Mitochondrial Metabolism as a Target for Counteraction.
CAR-T Cell Exhaustion in Cancer over the Past Decade: Mitochondrial Metabolism as a Target for Counteraction.
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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。
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.
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