Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches.

中文翻译：

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PD-1/PD-L1在癌症中的调控机制


免疫逃避有助于癌症的生长和进展。癌细胞能够激活具有免疫抑制功能的不同免疫检查点途径。程序性死亡蛋白1（PD-1）和程序性细胞死亡配体（PD-L）被认为是主要的免疫检查点分子。 PD-1和PD-L1的相互作用主要通过抑制效应T细胞的活性同时增强免疫抑制调节性T细胞（Treg）的功能来负向调节适应性免疫反应，在很大程度上有助于维持免疫稳态，防止免疫失调和有害的免疫反应。然而，癌细胞利用 PD-1/PD-L1 轴导致癌症发生和进展过程中的免疫逃逸。通过中和抗体阻断PD-1/PD-L1可恢复T细胞活性并增强抗肿瘤免疫力，在癌症治疗中取得了显着的成功。因此，PD-1/PD-L1在癌症中的调控机制越来越受到人们的关注。本文旨在全面综述 PD-1/PD-L1 信号在人类自身免疫性疾病和癌症中的作用。我们总结了癌症中 PD-1 和 PD-L1 表达和活性的调控机制的各个方面，包括遗传、表观遗传、转录后和翻译后调控机制。此外，我们进一步总结了针对PD-1/PD-L1抗体单独和联合其他治疗方法抗肿瘤作用的临床研究进展，为寻找新的肿瘤标志物和开发联合治疗方法提供新策略。