Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Int Immunol. 2022 Oct 5;34(11):571-577. doi: 10.1093/intimm/dxac038.
Persistent antigenic stimulation results in loss of effector function or physical deletion of antigen-specific CD8 T cells. This T-cell state is called T-cell exhaustion and occurs during chronic infection and cancer. Antigen-specific CD8 T cells during T-cell exhaustion express the inhibitory receptor PD-1, the expression of which plays a major role in T-cell dysfunction. PD-1 blockade re-invigorates CD8 T-cell immunity and has been proven effective against many different types of human cancer. To further improve the efficacy of PD-1-targeted immunotherapy in cancer patients, a better understanding of T-cell exhaustion is required. Recent studies have revealed that antigen-specific CD8 T cells during T-cell exhaustion are heterogeneous and have also uncovered the detailed mechanisms for PD-1-targeted immunotherapy. Here, we review the CD8 T-cell subsets that arise during T-cell exhaustion, the lineage relationship among these individual subsets and the role of each subset in PD-1 blockade. Also, we discuss potential strategies to enhance the efficacy of PD-1-targeted immunotherapy.
持续的抗原刺激会导致效应功能丧失或抗原特异性 CD8 T 细胞的物理缺失。这种 T 细胞状态称为 T 细胞耗竭，发生在慢性感染和癌症中。T 细胞耗竭期间的抗原特异性 CD8 T 细胞表达抑制性受体 PD-1，其表达在 T 细胞功能障碍中起主要作用。PD-1 阻断重新激活 CD8 T 细胞免疫，已被证明对多种不同类型的人类癌症有效。为了进一步提高癌症患者 PD-1 靶向免疫治疗的疗效，需要更好地了解 T 细胞耗竭。最近的研究揭示了 T 细胞耗竭期间抗原特异性 CD8 T 细胞的异质性，并揭示了 PD-1 靶向免疫治疗的详细机制。在这里，我们综述了 T 细胞耗竭过程中出现的 CD8 T 细胞亚群、这些亚群之间的谱系关系以及每个亚群在 PD-1 阻断中的作用。此外，我们还讨论了增强 PD-1 靶向免疫治疗疗效的潜在策略。
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