PD-L1: expression regulation

Abstract

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.

Keywords: Drug discovery; Epigenetics; Immune checkpoint blockage; Immunotherapy; PD-L1 expression.

Figure 1.

The enhancement effect of antibodies targeting PD-1 and PD-L1 on T cells killing tumor cells. PD-1 = programmed cell death-1, PD-L1 = programmed death-ligand 1.

Figure 2.

The regulatory mechanism of PD-L1 expression. PD-L1 = programmed death-ligand 1.