造血干细胞 (HSC) 和 T 细胞是密切相关的谱系依赖性细胞群，广泛用作治疗血液恶性肿瘤和某些类型实体瘤的治疗产品。这些细胞疗法可以挽救生命；然而，它们的功效常常受到影响其活性和细胞特性的因素的限制。这些因素中包括线粒体代谢，它影响 HSC 和 T 细胞的功能和命运。线粒体除了是“细胞发电站”之外，还提供代谢中间体，用作表观遗传修饰和染色质重塑的底物，从而驱动分化过程中的细胞命运决定。此外，线粒体健康和线粒体质量控制机制与细胞功能密切相关，这些线粒体特性的损害与 T 细胞耗竭和衰老等因素导致的细胞功能障碍相关。在这里，我们概述了线粒体在塑造这些谱系相关细胞群的行为中的作用。此外，我们讨论了新型线粒体靶向策略在增强基于 HSC 和 T 细胞的癌症免疫疗法方面的潜力，并强调了此类方法的设计和应用如何需要考虑 HSC 和 T 细胞之间代谢的相似性和差异。请参阅第 14 页的相关文章。 1302.©2023 美国癌症研究协会。

Hematopoietic stem cells (HSC) and T cells are intimately related, lineage-dependent cell populations that are extensively used as therapeutic products for the treatment of hematologic malignancies and certain types of solid tumors. These cellular therapies can be life-saving treatments; however, their efficacies are often limited by factors influencing their activity and cellular properties. Among these factors is mitochondrial metabolism, which influences the function and fate commitment of both HSCs and T cells. Mitochondria, besides being the "cellular powerhouse," provide metabolic intermediates that are used as substrates for epigenetic modifications and chromatin remodeling, thus, driving cell fate decisions during differentiation. Moreover, mitochondrial fitness and mitochondrial quality control mechanisms are closely related to cellular function, and impairment of these mitochondrial properties associates with cellular dysfunction due to factors such as T-cell exhaustion and aging. Here, we give an overview of the role of mitochondria in shaping the behavior of these lineage-related cell populations. Moreover, we discuss the potential of novel mitochondria-targeting strategies for enhancing HSC- and T cell-based cancer immunotherapies and highlight how design and application of such approaches requires consideration of the metabolic similarities and differences between HSCs and T cells. See related article on p. 1302.©2023 American Association for Cancer Research.