《生命科学》 2023, 35(3): 367-377
程序性死亡配体PD-L1在肿瘤中调控机制的研究进展
摘 要：
肿瘤新发病例逐年增长，严重影响居民身体健康并带来了沉重的医疗负担。肿瘤免疫治疗近年来异军突起，目前肿瘤免疫治疗的主要思路是通过抑制剂或对应抗体来干扰PD-1/PD-L1 轴，从而解除对T细胞免疫状态的抑制，发挥杀伤肿瘤细胞的功能，因此以PD-1/PD-L1 为靶点的免疫调节对抗肿瘤有重要意义。PD-L1 通常在各种恶性肿瘤中表达上调，最新证据表明存在多种潜在机制或信号通路调控PD-L1 表达，基于此开发特异的小分子抑制剂在抑制关键致癌信号通路的同时，还能抑制PD-L1 表达，从而实现免疫检查点抑制剂联合靶向药物疗法的突破，发挥协同抗肿瘤效应。本文就癌症中PD-L1 在基因突变、表观遗传修饰、转录和翻译后修饰水平的调控机制展开论述，为进一步开展联合靶向疗法提供理论基础。
通讯作者：谢 妮 , Email:xn100@szu.edu.cn
Abstract:
The incidence of cancer is increasing yearly, which seriously affects the health of residents and brings about a heavy medical burden. Tumor immunotherapy has acquired momentum in recent years. At present, the main idea of tumor immunotherapy is to interfere with the PD-1/PD-L1 axis by inhibitors or corresponding antibodies, to remove the immune-suppressed status of T cells and kill tumor cells. Therefore, it is of great significance to fight against tumors by targeting PD-1/PD-L1 for immune regulation. PD-L1 is typically high-expressed in all malignant tumors, and many potential mechanisms or signaling pathways regulate PD-L1 expression. The immune checkpoint inhibitors, combined with targeted drug therapy, can exert a synergistic anti-tumor effect based on the role of specific small molecule inhibitors to inhibit key signaling pathways and the expression of PD-L1 simultaneously. This article reviews the effects of gene mutations, epigenetic modifications, transcriptional regulation and posttranslational modification on PD-L1 in cancer, aiming to provide a theoretical basis for further development of combined targeted therapy.
Communication Author：XIE Ni , Email:xn100@szu.edu.cn
