PD-L1表达调控与肿瘤免疫治疗的研究进展

Research progress of PD-L1 expression regulation and tumor immunotherapy

程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)/程序性死亡配体1(programmed death-ligand 1,PD-L1)是导致肿瘤免疫逃逸的重要免疫检查点分子,阻断PD-1/PD-L1可以重新激活细胞毒性T细胞对肿瘤的杀伤作用,是一种重要的肿瘤免疫治疗方式。肿瘤细胞中PD-L1的表达可能影响抗PD-1/PD-L1治疗的临床疗效。因此,了解PD-L1表达调控的分子机制有助于指导PD-1/PD-L1相关免疫检查点抑制剂在临床中的应用。PD-L1的表达调控涉及染色质和基因组的改变、转录及转录后调控、翻译水平调控和翻译后修饰等。此外,肿瘤微环境中的多种因素也可以诱导肿瘤细胞中PD-L1的表达。文章系统地讨论了肿瘤中PD-L1调控的机制,并分析了其对于肿瘤免疫治疗的意义。

Programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)are important immune checkpoint molecules leading to tumor immune escape.Blocking PD-1/PD-L1 can reactivate the killing effect of cytotoxic T cells on tumor,which is an important way of tumor immunotherapy.The expression of PD-L1 in tumor cells may affect the clinical efficacy of anti-PD-1/PD-L1 therapy.Therefore,understanding the molecular mechanism of PD-L1 expression regulation is helpful to guide the clinical application of PD-1/PD-L1 related immune checkpoint inhibitors.Regulation of PD-L1 expression involves chromatin and genomic changes,transcriptional and post transcriptional regulation,translational regulation and post translational modification.In addition,various factors in tumor microenvironment can also induce the expression of PD-L1 in tumor cells.This review systematically discussed the mechanism of PD-L1 regulation in tumor and analyzed its significance for tumor immunotherapy.