Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA; email:
Department of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, USA; email:
Annu Rev Med. 2018 Jan 29;69:301-318. doi: 10.1146/annurev-med-012017-043208.
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.
抗原特异性 CD8 T 细胞是控制慢性感染和癌症的关键，但持续的抗原刺激会导致 T 细胞衰竭。衰竭的 CD8 T 细胞效应功能和增殖能力下降，部分原因是抑制性受体（如程序性细胞死亡 (PD)-1）的过度表达。阻断 PD-1 通路为增强 T 细胞反应开辟了新的治疗途径，对癌症患者尤其有益。目前正在评估许多其他策略来恢复衰竭的 CD8 T 细胞的功能，其中许多与 PD-1 靶向治疗相结合。衰竭的 CD8 T 细胞包含具有独特分化和功能状态的异质性细胞群体。最近描述了一个负责 PD-1 治疗后增殖爆发的干细胞样 PD-1 CD8 T 细胞亚群。为了建立合理的免疫治疗干预措施，迫切需要更深入地了解 T 细胞衰竭。
