Glioblastomas Acquire Myeloid-affiliated Transcriptional Programs Via Epigenetic Immunoediting to Elicit Immune Evasion

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2021 Apr 15

PMID 33857425

Citations 148

Authors

Ester Gangoso

Benjamin Southgate

Leanne Bradley

Stefanie Rus

Felipe Galvez-Cancino

Niamh McGivern

Esra Guc

Chantriolnt-Andreas Kapourani

Adam Byron

Kirsty M Ferguson

Neza Alfazema

Gillian Morrison

Vivien Grant

Carla Blin

IengFong Sou

Maria Angeles Marques-Torrejon

Lucia Conde

Simona Parrinello

Javier Herrero

Stephan Beck

Sebastian Brandner

Paul M Brennan

Paul Bertone

Jeffrey W Pollard

Sergio A Quezada

Duncan Sproul

Margaret C Frame

Alan Serrels

Steven M Pollard

Affiliations

Soon will be listed here.

Abstract

Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, we uncover an acquired capability of GSCs to escape immune clearance by establishing an enhanced immunosuppressive tumor microenvironment. Mechanistically, this is not elicited via genetic selection of tumor subclones, but through an epigenetic immunoediting process wherein stable transcriptional and epigenetic changes in GSCs are enforced following immune attack. These changes launch a myeloid-affiliated transcriptional program, which leads to increased recruitment of tumor-associated macrophages. Furthermore, we identify similar epigenetic and transcriptional signatures in human mesenchymal subtype GSCs. We conclude that epigenetic immunoediting may drive an acquired immune evasion program in the most aggressive mesenchymal GBM subtype by reshaping the tumor immune microenvironment.

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