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PD‐L1 methylation regulates PD‐L1 expression and is associated with melanoma survival
Author(s) -
Micevic Goran,
Thakral Durga,
McGeary Meaghan,
Bosenberg Marcus W.
Publication year - 2019
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12745
Subject(s) - epigenetics , dna methylation , methylation , melanoma , cancer research , cpg site , immune checkpoint , biology , immunotherapy , immunology , gene expression , genetics , immune system , gene
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.