PD-L1 methylation regulates PD-L1 expression and is associated with melanoma survival

Pigment Cell Melanoma Res. 2019 May;32(3):435-440. doi: 10.1111/pcmr.12745. Epub 2018 Nov 22.

Abstract

The aim of this study is to determine the significance of programmed death ligand 1 (PD-L1 or CD274) methylation in relation to PD-L1 expression and survival in melanoma. Despite the clinical importance of therapies targeting the PD-1/PD-L1 immune checkpoint in melanoma, factors regulating PD-L1 expression, including epigenetic mechanisms, are not completely understood. In this study, we examined PD-L1 promoter methylation in relation to PD-L1 expression and overall survival in melanoma patients. Our results suggest that DNA methylation regulates PD-L1 expression in melanoma, and we identify the key methylated CpG loci in the PD-L1 promoter, establish PD-L1 methylation as an independent survival prognostic factor, provide proof of concept for altering PD-L1 expression by hypomethylating agents, and uncover that PD-L1 methylation is associated with an interferon signaling transcriptional phenotype. Based on our findings, measuring and altering PD-L1 promoter DNA methylation may have potential prognostic and therapeutic applications in melanoma.

Keywords: DNA methylation; PD-L1; epigenetics; melanoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / analysis*
  • Cohort Studies
  • DNA Methylation*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / mortality*
  • Melanoma / pathology
  • Prognosis
  • Promoter Regions, Genetic
  • Survival Rate

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human