Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Semin Cancer Biol. 2022 Oct;85:246-252. doi: 10.1016/j.semcancer.2021.04.002. Epub 2021 Apr 5.
Antibodies targeting programmed cell death protein 1 (PD-1) or its ligand programmed death-ligand 1 (PD-L1) are profoundly changing the methods to treat cancers with long-term clinical benefits. Unlike conventional methods that directly target tumor cells, PD-1/PD-L1 blockade exerts anti-tumor effects largely through reactivating or normalizing cytotoxic T lymphocyte in the tumor microenvironment to combat cancer cells. However, only a small fraction of cancer patients responds well to PD-1/PD-L1 blockade and clinical outcomes have reached a bottleneck without substantial advances. Therefore, better understanding the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated will provide new insights to improve the efficacy of current anti-PD-1/PD-L1 therapy. Here, we provide an update of current progress of PD-L1 and PD-1 post-translational regulations and highlight the mechanism-based combination therapy strategies for a better treatment of human cancer.
针对程序性细胞死亡蛋白 1（PD-1）或其配体程序性死亡配体 1（PD-L1）的抗体正在深刻改变治疗癌症的方法，为患者带来长期的临床获益。与直接针对肿瘤细胞的传统方法不同，PD-1/PD-L1 阻断主要通过在肿瘤微环境中重新激活或使细胞毒性 T 淋巴细胞正常化来发挥抗肿瘤作用，从而对抗癌细胞。然而，只有一小部分癌症患者对 PD-1/PD-L1 阻断反应良好，并且在没有实质性进展的情况下，临床结果已经达到了瓶颈。因此，更好地了解 PD-1/PD-L1 表达如何受到调控的分子机制将为提高当前抗 PD-1/PD-L1 治疗的疗效提供新的见解。在这里，我们提供 PD-L1 和 PD-1 翻译后调控的最新进展，并强调基于机制的联合治疗策略，以更好地治疗人类癌症。
