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...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.展开更多
基金the Support Project of High-level Teachers in 517 Beijing Municipal Universities in the Period of 13th Five-year Plan(IDHT20190510)518the National Natural Science Foundation of China(81972652).
文摘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.
