Antigen-specific CD8 T cells are central to the control of chronic infections and cancer, but persistent antigen stimulation results in T cell exhaustion. Exhausted CD8 T cells have decreased effector function and proliferative capacity, partly caused by overexpression of inhibitory receptors such as programmed cell death (PD)-1. Blockade of the PD-1 pathway has opened a new therapeutic avenue for reinvigorating T cell responses, with positive outcomes especially for patients with cancer. Other strategies to restore function in exhausted CD8 T cells are currently under evaluation—many in combination with PD-1-targeted therapy. Exhausted CD8 T cells comprise heterogeneous cell populations with unique differentiation and functional states. A subset of stem cell–like PD-1⁺ CD8 T cells responsible for the proliferative burst after PD-1 therapy has been recently described. A greater understanding of T cell exhaustion is imperative to establish rational immunotherapeutic interventions.

中文翻译：

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慢性感染和癌症中的CD8 T细胞衰竭：干预的机会。

抗原特异性CD8 T细胞对于控制慢性感染和癌症至关重要，但是持续的抗原刺激会导致T细胞衰竭。耗尽的CD8 T细胞具有降低的效应子功能和增殖能力，部分原因是抑制性受体的过度表达，例如程序性细胞死亡（PD）-1。PD-1途径的阻断为重振T细胞反应开辟了一条新的治疗途径，尤其是对于癌症患者，其取得了积极的成果。目前正在评估恢复用尽的CD8 T细胞功能的其他策略-许多与PD-1靶向疗法联合使用。耗尽的CD8 T细胞包含具有独特分化和功能状态的异种细胞群体。干细胞样PD-1 ^+的子集最近已经描述了负责PD-1治疗后增殖爆发的CD8 T细胞。必须建立合理的免疫治疗干预措施，以更好地理解T细胞衰竭。