Immune checkpoint blockade therapy has revolutionized cancer treatment, but resistance remains prevalent, often due to dysfunctional tumor-infiltrating lymphocytes. A key contributor to this dysfunction is mitochondrial dysfunction, characterized by defective oxidative phosphorylation, impaired adaptation, and depolarization, which promotes T cell exhaustion and severely compromises antitumor efficacy. This review summarizes recent advances in restoring the function of exhausted T cells through mitochondria-targeted strategies, such as metabolic remodeling, enhanced biogenesis, and regulation of antioxidant and reactive oxygen species, with the aim of reversing the state of T cell exhaustion and improving the response to immunotherapy. A deeper understanding of the role of mitochondria in T cell exhaustion lays the foundation for the development of novel mitochondria-targeted therapies and opens a new chapter in cancer immunotherapy.

中文翻译：

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靶向线粒体：恢复耗竭 T 细胞的抗肿瘤功效


免疫检查点阻断疗法彻底改变了癌症治疗，但耐药性仍然普遍存在，这通常是由于肿瘤浸润淋巴细胞功能失调。这种功能障碍的一个关键因素是线粒体功能障碍，其特征是氧化磷酸化缺陷、适应受损和去极化，这会促进 T 细胞耗竭并严重损害抗肿瘤疗效。本文总结了通过线粒体靶向策略恢复耗竭 T 细胞功能的最新进展，例如代谢重塑、增强生物发生以及调节抗氧化和活性氧，目的是逆转 T 细胞耗竭的状态并改善对免疫治疗的反应。更深入地了解线粒体在 T 细胞耗竭中的作用，为开发新型线粒体靶向疗法奠定了基础，并开启了癌症免疫疗法的新篇章。