Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, United Kingdom.
Front Immunol. 2020 Oct 21;11:568931. doi: 10.3389/fimmu.2020.568931. eCollection 2020.
Programmed death-ligand 1 (PD-L1) is an immune checkpoint inhibitor that binds to its receptor PD-1 expressed by T cells and other immune cells to regulate immune responses; ultimately preventing exacerbated activation and autoimmunity. Many tumors exploit this mechanism by overexpressing PD-L1 which often correlates with poor prognosis. Some tumors have also recently been shown to express PD-1. On tumors, PD-L1 binding to PD-1 on immune cells promotes immune evasion and tumor progression, primarily by inhibition of cytotoxic T lymphocyte effector function. PD-1/PD-L1-targeted therapy has revolutionized the cancer therapy landscape and has become the first-line treatment for some cancers, due to their ability to promote durable anti-tumor immune responses in select patients with advanced cancers. Despite this clinical success, some patients have shown to be unresponsive, hyperprogressive or develop resistance to PD-1/PD-L1-targeted therapy. The exact mechanisms for this are still unclear. This review will discuss the current status of PD-1/PD-L1-targeted therapy, oncogenic expression of PD-L1, the new and emerging tumor-intrinisic roles of PD-L1 and its receptor PD-1 and how they may contribute to tumor progression and immunotherapy responses as shown in different oncology models.
程序性死亡配体 1（PD-L1）是一种免疫检查点抑制剂，可与 T 细胞和其他免疫细胞表达的受体 PD-1 结合，从而调节免疫反应；最终防止过度激活和自身免疫。许多肿瘤通过过度表达 PD-L1 来利用这种机制，而 PD-L1 的过度表达通常与预后不良相关。最近还发现一些肿瘤表达 PD-1。在肿瘤上，PD-L1 与免疫细胞上的 PD-1 结合可促进免疫逃逸和肿瘤进展，主要通过抑制细胞毒性 T 淋巴细胞效应功能。PD-1/PD-L1 靶向治疗彻底改变了癌症治疗领域，并已成为某些癌症的一线治疗方法，因为它们能够在某些晚期癌症患者中促进持久的抗肿瘤免疫反应。尽管取得了这一临床成功，但一些患者表现出无反应、超进展或对 PD-1/PD-L1 靶向治疗产生耐药性。其确切机制尚不清楚。本文将讨论 PD-1/PD-L1 靶向治疗的现状、PD-L1 的致癌表达、PD-L1 及其受体 PD-1 的新的和新兴的肿瘤内在作用，以及它们如何在不同的肿瘤模型中促进肿瘤进展和免疫治疗反应。
