Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
Ophthalmology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
Front Immunol. 2023 Jul 24;14:1230135. doi: 10.3389/fimmu.2023.1230135. eCollection 2023.
The immune checkpoint molecules programmed cell death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) are one of the most promising targets for tumor immunotherapy. PD-L1 is overexpressed on the surface of tumor cells and inhibits T cell activation upon binding to PD⁃1 on the surface of T cells, resulting in tumor immune escape. The therapeutic strategy of targeting PD-1/PD-L1 involves blocking this binding and restoring the tumor-killing effect of immune cells. However, in clinical settings, a relatively low proportion of cancer patients have responded well to PD-1/PD-L1 blockade, and clinical outcomes have reached a bottleneck and no substantial progress has been made. In recent years, PD-L1 post-translation modifications (PTMs) have gradually become a hot topic in the field of PD-L1 research, which will provide new insights to improve the efficacy of current anti-PD-1/PD-L1 therapies. Here, we summarized and discussed multiple PTMs of PD-L1, including glycosylation, ubiquitination, phosphorylation, acetylation and palmitoylation, with a major emphasis on mechanism-based therapeutic strategies (including relevant enzymes and targets that are already in clinical use and that may become drugs in the future). We also summarized the latest research progress of PTMs of PD-L1/PD-1 in regulating immunotherapy. The review provided novel strategies and directions for tumor immunotherapy research based on the PTMs of PD-L1/PD-1.
免疫检查点分子程序性细胞死亡受体 1（PD-1）和程序性死亡配体 1（PD-L1）是肿瘤免疫治疗最有前途的靶点之一。PD-L1 在肿瘤细胞表面过表达，与 T 细胞表面的 PD-1 结合后抑制 T 细胞激活，导致肿瘤免疫逃逸。靶向 PD-1/PD-L1 的治疗策略涉及阻断这种结合，恢复免疫细胞的杀伤作用。然而，在临床环境中，相对较低比例的癌症患者对 PD-1/PD-L1 阻断反应良好，临床结果已达到瓶颈，没有取得实质性进展。近年来，PD-L1 的翻译后修饰（PTMs）逐渐成为 PD-L1 研究领域的热点，这将为提高当前抗 PD-1/PD-L1 治疗的疗效提供新的见解。在这里，我们总结和讨论了 PD-L1 的多种 PTMs，包括糖基化、泛素化、磷酸化、乙酰化和棕榈酰化，主要强调基于机制的治疗策略（包括已在临床使用和未来可能成为药物的相关酶和靶点）。我们还总结了 PD-L1/PD-1 PTMs 在调节免疫治疗中的最新研究进展。该综述为基于 PD-L1/PD-1 的 PTMs 的肿瘤免疫治疗研究提供了新的策略和方向。
