Epigenetics in modulating immune functions of stromal and immune cells in the tumor microenvironment.

Cellular & Molecular Immunology
Xingyi Pan, Lei Zheng

Abstract

Epigenetic regulation of gene expression in cancer cells has been extensively studied in recent decades, resulting in the FDA approval of multiple epigenetic agents for treating different cancer types. Recent studies have revealed novel roles of epigenetic dysregulation in altering the phenotypes of immune cells and tumor-associated stromal cells, including fibroblasts and endothelial cells. As a result, epigenetic dysregulation of these cells reshapes the tumor microenvironment (TME), changing it from an antitumor environment to an immunosuppressive environment. Here, we review recent studies demonstrating how specific epigenetic mechanisms drive aspects of stromal and immune cell differentiation with implications for the development of solid tumor therapeutics, focusing on the pancreatic ductal adenocarcinoma (PDA) TME as a representative of solid tumors. Due to their unique ability to reprogram the TME into a more immunopermissive environment, epigenetic agents have great potential for sensitizing cancer immunotherapy to augment the antitumor response, as an immunopermissive TME is a prerequisite for the success of cancer immunotherapy but is often not developed with solid tumors. The idea of combining epigenetic agents with...Continue Reading

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Citations

Jan 26, 2021·Journal of Biochemical and Molecular Toxicology·Keywan Mortezaee
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Jenniffer LinaresAlexandre Calon
Feb 17, 2021·Cellular Immunology·Maria Dulfary Sanchez-PinoAugusto C Ochoa
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Sep 1, 2021·Journal of Biochemical and Molecular Toxicology·Masoud NajafiKeywan Mortezaee

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Methods Mentioned

BETA
xenografts
histone acetylation
immunoprecipitation
acetylation
xenograft
methylation profiling
transgenic

Clinical Trials Mentioned

NCT02437136
NCT02638090
NCT02512172
NCT03264404
NCT03854474
NCT03590054
NCT03250273
NCT01928576
NCT02635061
NCT02032810

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