Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Medical Genetics Research Center, Student Research Committee, Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Immunogenetics. 2018 Feb;70(2):73-86. doi: 10.1007/s00251-017-1015-5. Epub 2017 Jun 22.
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers. In particular, PD-1 over-expression influences tumor-specific T cell immunity in a cancer microenvironment. Blocking the PD-1/PD-1 ligand (PD-L1) pathway could potentially augment endogenous antitumor responses. Along these lines, the use of PD-1/PD-L1 inhibitors has been applied in clinical trials against diverse forms of cancer. It was believed that antibodies targeting PD-1/PD-L1 might synergize with other treatments that enhance endogenous antitumor immunity by blocking inhibitory receptor-ligand interactions. However, in all cases, the host genetic status (as well as that of the tumor) is likely to have an impact on the expected outcomes. Various investigations have evaluated the association between PD-1 polymorphisms and the risk of various types of cancer. Frequently studied PD-1 polymorphisms, PD-1.1 (rs36084323), PD-1.3 (rs11568821), PD-1.5 (rs2227981), PD-1.9 (rs2227982), and PD-1 rs7421861, and their associations in the risk of susceptibility to different types of cancer are mentioned in this review, as are studies highlighting the significance of conducting genetic association studies in different ethnic populations.
程序性细胞死亡蛋白 1（PD-1）由激活的 T 细胞表达，作为一种免疫调节分子，负责 T 细胞激活和外周耐受的负调节。PD-1 基因还编码一种抑制性细胞表面受体，参与免疫反应/耐受过程中 T 细胞功能的调节。除了对 T 细胞具有强大的抑制作用外，PD-1 还在调节 B 细胞和单核细胞反应中发挥作用。据报道，PD-1 的过度表达有助于不同癌症中的免疫系统逃避。特别是，PD-1 的过度表达会影响肿瘤特异性 T 细胞免疫在癌症微环境中。阻断 PD-1/PD-1 配体（PD-L1）途径可能潜在地增强内源性抗肿瘤反应。沿着这些思路，PD-1/PD-L1 抑制剂的使用已应用于针对各种形式癌症的临床试验中。人们认为，针对 PD-1/PD-L1 的抗体可能与通过阻断抑制性受体-配体相互作用增强内源性抗肿瘤免疫的其他治疗方法协同作用。然而，在所有情况下，宿主遗传状态（以及肿瘤的遗传状态）可能对预期结果产生影响。各种研究评估了 PD-1 多态性与各种类型癌症风险之间的关系。经常研究的 PD-1 多态性，PD-1.1（rs36084323）、PD-1.3（rs11568821）、PD-1.5（rs2227981）、PD-1.9（rs2227982）和 PD-1 rs7421861，以及它们在不同类型癌症易感性风险中的关联在本综述中提到，同时还强调了在不同种族人群中进行遗传关联研究的重要性。
