经过三十年的基础研究，对促进T细胞耗竭的分子和细胞机制进行了探讨，并且现在可以合理设计基于T细胞的治疗方法治疗慢性感染和癌症。曾经以静态细胞命运描述，现在已经充分认识到朝向耗竭的发展途径由具有不同效应潜力的细胞异质性池组成，最终趋于一个末端分化状态。最近对T细胞耗竭分化轨迹上的发育阶段进行描述，为过去的免疫治疗成功和未来的机会提供了洞见。在这里，我们讨论了在T细胞功能失调途径上发生的不同发育阶段的特征以及这些不同的CD8+ T细胞命运对癌症免疫治疗的影响。

Thirty years of foundational research investigating molecular and cellular mechanisms promoting T cell exhaustion are now enabling rational design of T cell-based therapies for the treatment of chronic infections and cancer. Once described as a static cell fate, it is now well appreciated that the developmental path toward exhaustion is composed of a heterogeneous pool of cells with varying degrees of effector potential that ultimately converge on a terminally differentiated state. Recent description of the developmental stages along the differentiation trajectory of T cell exhaustion has provided insight into past immunotherapeutic success and future opportunities. Here, we discuss the hallmarks of distinct developmental stages occurring along the path to T cell dysfunction and the impact of these discrete CD8+ T cell fates on cancer immunotherapy.