Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nat Rev Immunol. 2018 Mar;18(3):153-167. doi: 10.1038/nri.2017.108. Epub 2017 Nov 13.
T cell activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential role in balancing protective immunity and immunopathology, homeostasis and tolerance. However, during responses to chronic pathogens and tumours, PD1 expression can limit protective immunity. Recently developed PD1 pathway inhibitors have revolutionized cancer treatment for some patients, but the majority of patients do not show complete responses, and adverse events have been noted. This Review discusses the diverse roles of the PD1 pathway in regulating immune responses and how this knowledge can improve cancer immunotherapy as well as restore and/or maintain tolerance during autoimmunity and transplantation.
T 细胞活化是一个高度调控的过程，涉及 T 细胞受体与肽-MHC 的结合以及正向协同刺激信号。在活化后，共抑制“检查点”，包括程序性细胞死亡蛋白 1（PD1），被诱导以调节 T 细胞。PD1 在平衡保护性免疫和免疫病理学、稳态和耐受方面发挥着重要作用。然而，在对慢性病原体和肿瘤的反应中，PD1 的表达可能会限制保护性免疫。最近开发的 PD1 通路抑制剂已彻底改变了一些患者的癌症治疗方法，但大多数患者并未表现出完全缓解，并且已经注意到不良反应。本综述讨论了 PD1 通路在调节免疫反应中的多种作用，以及如何利用这些知识来改善癌症免疫疗法，并在自身免疫和移植过程中恢复和/或维持耐受。
