程序性细胞死亡蛋白1配体1(PD-L1)的翻译后修饰调控及其在肿瘤免疫治疗中的应用进展  

Regulation of PD-L1 posttranslational modification and its application progress in tumor immunotherapy

作　　者：苏媛媛 王秦豪 茹懿 董健 李霞 张正祥 SU Yuanyuan;WANG Qinhao;RU Yi;DONG Jian;LI Xia;ZHANG Zhengxiang(Department of pharmacology,Medical College,Yan'an University,Yan'an 716000;State Key Laboratory of Cancer Biology,Department of Biochemistry and Molecular Biology,Collge of Basic Medicine,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]延安大学医学院药理学教研室,陕西延安716000 [2]空军军医大学基础医学院生物化学与分子生物学教研室,肿瘤生物学国家重点实验室,陕西西安710032

出　　处：《细胞与分子免疫学杂志》2022年第11期1036-1043,共8页Chinese Journal of Cellular and Molecular Immunology

基　　金：延安大学科研计划项目(YDY2020-21)。

摘　　要：程序性细胞死亡蛋白1配体1/程序性细胞死亡蛋白1(PD-L1/PD-1)免疫检查点是最有前景的肿瘤免疫治疗靶点之一。肿瘤等细胞表面过度表达的PD-L1通过与T细胞表面的PD-1结合,抑制T细胞活化,导致肿瘤免疫逃逸;靶向PD-1/PD-L1的治疗策略主要通过阻断二者结合,恢复免疫细胞对肿瘤的杀伤作用。肿瘤细胞中PD-L1的水平与功能受到多层次的调控,其中,PD-L1的翻译后修饰(PTM)近年来备受关注,主要包括糖基化、磷酸化、泛素化、乙酰化以及棕榈酰化修饰等,这些修饰方式能够影响PD-L1的稳定性、细胞内定位或功能,进而调控T细胞活化和肿瘤免疫,因而干预PD-L1的PTM亦可作为新的抗肿瘤免疫逃逸治疗手段。The immune checkpoint, programmed death 1 ligand-1/programmed death-1(PD-L1/PD-1), is one of the most promising targets for tumor immunotherapy. Overexpressed PD-L1 on the surface of tumor cells could bind to PD-1 on the surface of T cells and inhibit the T cell activation, triggering tumor-immune-escape;therapeutic strategies targeting PD-1/PD-L1 restore the cytotoxic function of immune cells in the tumors by blocking PD-1/PD-L1 interaction. The PD-L1 undergoes multi-level regulations in tumor cells. Among them, post-translational modifications(PTMs) of PD-L1 mainly including glycosylation, phosphorylation, ubiquitination, acetylation and palmitoylation, have attracted much attention in recent years. These modifications directly affect the stability, cellular localization and function of PD-L1, and subsequently regulate the T cell activation and tumor immunity. Therefore, intervention with PTMs of PD-L1 may serve as a new approach for anti-tumor immunity-escape therapy.

关 键 词：肿瘤免疫治疗 程序性细胞死亡蛋白1配体1(PD-L1) 翻译后修饰 综述 

分 类 号：R457.2[医药卫生—治疗学] R392.11[医药卫生—临床医学] C353.11[社会学]