Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma.

Molecular Oncology
Shamik MitraGöran Jönsson

Abstract

The presence of immune cells in the tumor microenvironment has been associated with response to immunotherapies across several cancer types, including melanoma. Despite its therapeutic relevance, characterization of the melanoma immune microenvironments remains insufficiently explored. To distinguish the immune microenvironment in a cohort of 180 metastatic melanoma clinical specimens, we developed a method using promoter CpG methylation of immune cell type-specific genes extracted from genome-wide methylation arrays. Unsupervised clustering identified three immune methylation clusters with varying levels of immune CpG methylation that are related to patient survival. Matching protein and gene expression data further corroborated the identified epigenetic characterization. Exploration of the possible immune exclusion mechanisms at play revealed likely dependency on MITF protein level and PTEN loss-of-function events for melanomas unresponsive to immunotherapies (immune-low). To understand whether melanoma tumors resemble other solid tumors in terms of immune methylation characteristics, we explored 15 different solid tumor cohorts from TCGA. Low-dimensional projection based on immune cell type-specific methylation revealed grou...Continue Reading

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Citations

Sep 18, 2020·Epigenomics·Ning KangFrancesco Crea
May 10, 2021·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Xiao-Qiong ChenYu Peng
Jul 21, 2021·Journal for Immunotherapy of Cancer·Katharina FilipskiPatrick N Harter
Jul 20, 2021·Cancer Biomarkers : Section a of Disease Markers·Seema KhadirnaikarSudhanshu Kumar Shukla
Aug 28, 2021·Cells·Emilio Francesco Giunta On Behalf Of Scito Youth

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