Nature Reviews Immunology ( IF 67.7 ) Pub Date : 2017-11-13 , DOI: 10.1038/nri.2017.108 Arlene H. Sharpe , Kristen E. Pauken
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.
中文翻译:
PD1抑制途径的多种功能
T细胞活化是一个高度调控的过程,涉及T细胞受体的肽-MHC参与和积极的共刺激信号。激活后,包括程序性细胞死亡蛋白1(PD1)在内的共抑制性“检查点”被诱导调节T细胞。PD1在平衡保护性免疫和免疫病理学,体内稳态和耐受性方面起着至关重要的作用。但是,在对慢性病原体和肿瘤的反应过程中,PD1的表达会限制保护性免疫。最近开发的PD1途径抑制剂已经彻底改变了某些患者的癌症治疗方法,但是大多数患者并未显示出完全的反应,并且已经注意到了不良事件。