Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Konoe-Cho, Sakyo-Ku, 606-8501, Kyoto, Japan.
Curr Top Microbiol Immunol. 2017;410:75-97. doi: 10.1007/82_2017_67.
Immunity developed to defend our bodies from foreign particles, including bacteria and viruses. Although effector cells responsible for acquired immunity, mainly T cells, and B cells, are able to distinguish self from non-self, they sometimes attack the body's tissues because of imperfect central tolerance. Several immune check points developed to limit overactivation of these cells. One of the most important immune checkpoints is programmed cell death-1 (PD-1), which is expressed mainly on activated lymphocytes. As its ligands (PD-Ls) are expressed widely in the body and affect the responses against self and foreign antigens, controlling PD-1/PD-L interactions enables the management of several immune-related diseases such as autoimmune disease, virus infection, and cancers. Currently, the strategy of PD-1/ PD-L1 blockade has already been applied to clinical cancer therapy, providing evidences that PD-1 signal is one of the main factors of cancer immune escape in humans. The dramatic efficacy of PD-1 blockade in cancer immunotherapy, promises the control of other immune diseases by PD-1 signal modulation. In this review, we summarize the history of PD-1, subsequent basic studies, and their application to the clinic.
免疫系统能够抵御外来物质（包括细菌和病毒）对身体的侵害。虽然负责获得性免疫的效应细胞（主要是 T 细胞和 B 细胞）能够区分自身和非自身，但由于中枢耐受不完善，它们有时会攻击身体组织。为了限制这些细胞的过度激活，开发了几种免疫检查点。其中最重要的免疫检查点之一是程序性细胞死亡受体 1（PD-1），它主要在活化的淋巴细胞上表达。由于其配体（PD-Ls）在体内广泛表达，影响自身和外来抗原的反应，因此控制 PD-1/PD-L 相互作用可以管理多种与免疫相关的疾病，如自身免疫性疾病、病毒感染和癌症。目前，PD-1/PD-L1 阻断策略已应用于临床癌症治疗，为 PD-1 信号是人类癌症免疫逃逸的主要因素之一提供了证据。PD-1 阻断在癌症免疫治疗中的显著疗效预示着通过 PD-1 信号调节可以控制其他免疫性疾病。在这篇综述中，我们总结了 PD-1 的历史、随后的基础研究及其在临床上的应用。
