Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou Key Laboratory of Endometrial Disease Prevention and Treatment Zhengzhou China, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; Key Laboratory of Henan Province for Drug Quality and Evaluation; Institute of Drug Discovery and Development; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450052, Henan, China.
Cell Mol Life Sci. 2022 Jul 11;79(8):413. doi: 10.1007/s00018-022-04431-x.
Cancer immunotherapy is a rapidly developing and effective method for the treatment of a variety of malignancies in recent years. As a significant immune checkpoint, programmed cell death 1 ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) play the most significant role in cancer immune escape and cancer immunotherapy. Though PD-L1 have become an important target for drug development and there have been various approved drugs and clinic trials targeting it, and various clinical response rate and adverse reactions prevent many patients from benefiting from it. In recent years, combination trials have become the main direction of PD-1/PD-L1 antibodies development. Here, we summarized PD-L1 biofunctions and key roles in various cancers along with the development of PD-L1 inhibitors. The regulators that are involved in controlling PD-L1 expression including post-translational modification, mRNA level regulation as well as degradation and exosome secretory pathway of PD-L1 were focused. This systematic summary may provide comprehensive understanding of different regulations on PD-L1 as well as a broad prospect for the search of the important regulator of PD-L1. The regulatory factors of PD-L1 can be potential targets for immunotherapy and increase strategies of immunotherapy in combination.
近年来，癌症免疫疗法是治疗多种恶性肿瘤的一种快速发展且有效的方法。程序性细胞死亡蛋白 1 配体 1（PD-L1）及其受体程序性细胞死亡蛋白 1（PD-1）作为重要的免疫检查点，在癌症免疫逃逸和癌症免疫治疗中发挥着最重要的作用。尽管 PD-L1 已成为药物开发的重要靶点，并且已经有各种针对它的批准药物和临床试验，但各种临床反应率和不良反应使许多患者无法从中受益。近年来，联合试验已成为 PD-1/PD-L1 抗体开发的主要方向。在这里，我们总结了 PD-L1 的生物功能及其在各种癌症中的关键作用，以及 PD-L1 抑制剂的发展。重点介绍了参与控制 PD-L1 表达的调节剂，包括翻译后修饰、mRNA 水平调节以及 PD-L1 的降解和外泌体分泌途径。这种系统的总结可以全面了解 PD-L1 的不同调节，并为寻找 PD-L1 的重要调节剂提供广阔的前景。PD-L1 的调节因子可以成为免疫疗法的潜在靶点，并增加联合免疫疗法的策略。
