Recent advances of molecular mechanisms of regulating PD-L1 expression in melanoma

Abstract

Melanoma is a highly invasive malignant tumor, metastasis can occur in the early stage of the tumor, and the prognosis of patients in the late stage is extremely poor. Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors have made a major breakthrough in cancer treatment, which makes the treatment of melanoma enter a new period. The expression of PD-L1 in melanoma is an important biomarker to predict the inhibitory response to the immune checkpoint and is considered to be an independent prognostic indicator of melanoma. Although the related immune checkpoint inhibitors have achieved some good results, the regulation of PD-L1 expression in melanoma is complex and contains multiple types, and few detailed summaries have been done on all types of regulation, so it is very important to explore the complicated regulation mechanism of PD-L1 in melanoma. In this review, we systematically summarize the latest progress on the mechanism of PD-L1 expression regulation in melanoma. The regulatory factors positively related to PD-L1 include internal factors, external induction, signal pathway, transcription factors, epigenetics (Hypomethylation, HDAC6), translation and post-translation levels, while factors negatively related to PD-L1 include microRNA and epigenetics (HDAC8). In addition, the regulation of PD-L1 on the exosome surface is mediated by IFN-γ and there is a positive correlation between them. We hope this review will lay a foundation for the development of more effective and less toxic drugs for immunotherapy of melanoma.

Keywords: Immune escape; Immunotherapy; Melanoma; Programmed death ligand 1; Regulation.