Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.
Immunology. 2022 Dec;167(4):471-481. doi: 10.1111/imm.13573. Epub 2022 Sep 20.
The immune checkpoint programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) are biologically important immunosuppressive molecules, and the PD-L1/PD-1-mediated signalling pathway is currently considered one of the main mechanisms of tumour escape immune surveillance. PD-L1 is highly expressed on the cytomembrane of tumour cell and binds to PD-1 receptor of activated T cells. This interaction activates PD-L1/PD-1 downstream signal transduction, inhibiting T cells anti-tumour activity. Therefore, inhibitors of PD-L1/PD-1 activation, showing significant efficacy in some types of tumours, have been widely approved in clinical tumour therapy. Recent research on PD-L1/PD-1 signalling pathway regulation has shown post-translational modifications (PTMs) form of PD-L1 or PD-1, including glycosylation, ubiquitination, phosphorylation, and acetylation, which may play an important role in PD-L1/PD-1 signalling pathway regulation and anti-tumour function of T cells. In this review, we focused on PTMs of PD-L1/PD-1 research and potential applications in tumour immunotherapy.
免疫检查点程序性死亡受体 1（PD-1）和程序性死亡配体 1（PD-L1）是生物学上重要的免疫抑制分子，PD-L1/PD-1 介导的信号通路目前被认为是肿瘤逃避免疫监视的主要机制之一。PD-L1 在肿瘤细胞膜上高度表达，并与活化 T 细胞上的 PD-1 受体结合。这种相互作用激活 PD-L1/PD-1 下游信号转导，抑制 T 细胞的抗肿瘤活性。因此，PD-L1/PD-1 激活抑制剂在某些类型的肿瘤中显示出显著疗效，已在临床肿瘤治疗中得到广泛批准。最近对 PD-L1/PD-1 信号通路调控的研究表明，PD-L1 或 PD-1 的翻译后修饰（PTMs）形式，包括糖基化、泛素化、磷酸化和乙酰化，可能在 PD-L1/PD-1 信号通路调控和 T 细胞的抗肿瘤功能中发挥重要作用。在这篇综述中，我们重点介绍了 PD-L1/PD-1 的 PTMs 研究及其在肿瘤免疫治疗中的潜在应用。
