Dataset Information

PD-L1 (CD274) and PD-L2 (PDCD1LG2) promoter methylation is associated with HPV infection and transcriptional repression in head and neck squamous cell carcinomas.

ABSTRACT:

Background

DNA methylation of the immune checkpoint gene PD-L1 has recently been shown to be associated with PD-L1 mRNA expression in various malignancies. This study aimed to investigate the association of PD-L1 and PD-L2 methylation with mRNA expression, immune cell infitration, protein expression and human papilloma virus (HPV) infection in head and neck squamous cell carcinoma (HNSCC) patients.

Results

DNA methylation of PD-L1 and PD-L2 correlates inversely with mRNA expression (PD-L1: p ≤ 0.002; PD-L2: p ≤ 0.014). Methylation of specific CpG-sites of both PD-L1 and PD-L2 were further significantly associated with HPV infection in the TCGA cohort. Immune cell infiltrates correlated significantly with PD-L1 and PD-L2 methylation. In the validation cohort, PD-L1 protein expression was associated with PD-L1 hypomethylation (p = 0.012).

Conclusions

DNA methylation of PD-L1 and PD-L2 is associated with transcriptional silencing and HPV infection in HNSCCs. Additional studies are warranted to test PD-L1 and PD-L2 methylation as predictive biomarkers for response to immunotherapies (e.g. pembrolizumab and nivolumab) that target the PD-L1/PD-L2/PD-1 immune checkpoint axis.

Materials and methods

PD-L1 and PD-L2 promoter methylation and its mRNA expression were analyzed based on Infinium HumanMethylation450 BeadChip and RNA-Seq (both Illumina, Inc.) data in a representative HNSCC patient cohort (n = 528) enrolled by The Cancer Genome Atlas (TCGA) Research Network. A validation cohort consisting of 168 HNSCC patients treated at the University Hospital Bonn was analyzed regarding PD-L1 and PD-L2 promoter methylation by means of methylation-specific quantitative real-time PCR. PD-L1 protein expression in the validation cohort was quantified via immunohistochemistry (PD-L1 antibody clone 22C3, Dako/Agilent Technologies, Inc.).

SUBMITTER: Franzen A

PROVIDER: S-EPMC5787495 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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<i>PD-L1</i> (<i>CD274</i>) and <i>PD-L2</i> (<i>PDCD1LG2</i>) promoter methylation is associated with HPV infection and transcriptional repression in head and neck squamous cell carcinomas.

Franzen Alina A Vogt Timo J TJ Müller Tim T Dietrich Jörn J Schröck Andreas A Golletz Carsten C Brossart Peter P Bootz Friedrich F Landsberg Jennifer J Kristiansen Glen G Dietrich Dimo D

Oncotarget 20171207 1

<h4>Background</h4>DNA methylation of the immune checkpoint gene <i>PD-L1</i> has recently been shown to be associated with PD-L1 mRNA expression in various malignancies. This study aimed to investigate the association of <i>PD-L1</i> and <i>PD-L2</i> methylation with mRNA expression, immune cell infitration, protein expression and human papilloma virus (HPV) infection in head and neck squamous cell carcinoma (HNSCC) patients.<h4>Results</h4>DNA methylation of <i>PD-L1</i> and <i>PD-L2</i> corre ...[more]

PMID: 29416641

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