Zhou Yu-Jie, Li Guoli, Wang Jiyin, Liu Mengyuan, Wang Zihan, Song Yu, Zhang Xulong, Wang Xi
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Blood Sci. 2023 Jan 13;5(2):77-91. doi: 10.1097/BS9.0000000000000149. eCollection 2023 Apr.
Programmed death-ligand 1 (PD-L1), expressed on the surface of tumor cells, can bind to programmed cell death-1 (PD-1) on T cells. The interaction of PD-1 and PD-L1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their apoptosis. Various cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T-cell immunity, and immunotherapies targeting the PD-1/PD-L1 axis have been shown to exert remarkable anti-tumor effects; however, not all tumor patients benefit from these therapies. Therefore, study of the mechanisms regulating PD-L1 expression are imperative. In this review, we explore regulation of PD-L1 expression in the contexts of gene transcription, signaling pathways, histone modification and remodeling, microRNAs, long noncoding RNAs, and post-translational modification. Current developments in studies of agents that block PD-L1 and correlations between immunotherapies targeting PD-1/PD-L1 and PD-L1 expression are also summarized. Our review will assist in understanding of PD-L1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy.
程序性死亡配体1(PD-L1)表达于肿瘤细胞表面,可与T细胞上的程序性细胞死亡蛋白1(PD-1)结合。PD-1与PD-L1的相互作用可通过降低T细胞活性并加速其凋亡来抑制T细胞反应。多种癌症均高表达PD-L1,并利用PD-L1/PD-1信号传导来逃避免疫系统的T细胞免疫,而针对PD-1/PD-L1轴的免疫疗法已显示出显著的抗肿瘤效果;然而,并非所有肿瘤患者都能从这些疗法中获益。因此,研究调控PD-L1表达的机制势在必行。在本综述中,我们探讨了基因转录、信号通路、组蛋白修饰与重塑、微小RNA、长链非编码RNA以及翻译后修饰等背景下PD-L1表达的调控。还总结了阻断PD-L1的药物研究的当前进展以及针对PD-1/PD-L1的免疫疗法与PD-L1表达之间的相关性。我们的综述将有助于理解PD-L1表达调控,并讨论已报道的研究结果在癌症诊断和免疫治疗中的意义。