Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion

Ester Gangoso; Benjamin Southgate; Leanne Bradley; Stefanie Rus; Felipe Galvez-Cancino; Niamh McGivern; Esra Güç; 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

doi:10.1016/j.cell.2021.03.023

Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion

Ester Gangoso, Benjamin Southgate, Leanne Bradley, Stefanie Rus, Felipe Galvez-Cancino, Niamh McGivern, Esra Güç, 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 BeckSebastian Brandner, Paul M Brennan, Paul Bertone, Jeffrey W Pollard, Sergio A Quezada, Duncan Sproul, Margaret C Frame, Alan Serrels, Steven M Pollard

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Journal	Cell
DOIs	https://doi.org/10.1016/j.cell.2021.03.023
Publication status	Published - 14 Apr 2021

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https://www.sciencedirect.com/science/article/pii/S0092867421003512?via%3Dihub

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Gangoso, E., Southgate, B., Bradley, L., Rus, S., Galvez-Cancino, F., McGivern, N., Güç, E., Kapourani, C-A., Byron, A., Ferguson, K. M., Alfazema, N., Morrison, G., Grant, V., Blin, C., Sou, I., Marques-Torrejon, M. A., Conde, L., Parrinello, S., Herrero, J., ... Pollard, S. M. (2021). Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion. Cell. https://doi.org/10.1016/j.cell.2021.03.023

@article{48f6e2529f9644fca732a5d4b750a1ee,

title = "Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion",

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.",

author = "Ester Gangoso and Benjamin Southgate and Leanne Bradley and Stefanie Rus and Felipe Galvez-Cancino and Niamh McGivern and Esra G{\"u}{\c c} and Chantriolnt-Andreas Kapourani and Adam Byron and Ferguson, {Kirsty M} and Neza Alfazema and Gillian Morrison and Vivien Grant and Carla Blin and IengFong Sou and Marques-Torrejon, {Maria Angeles} and Lucia Conde and Simona Parrinello and Javier Herrero and Stephan Beck and Sebastian Brandner and Brennan, {Paul M} and Paul Bertone and Pollard, {Jeffrey W} and Quezada, {Sergio A} and Duncan Sproul and Frame, {Margaret C} and Alan Serrels and Pollard, {Steven M}",

year = "2021",

month = apr,

day = "14",

doi = "10.1016/j.cell.2021.03.023",

language = "English",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

}

Gangoso, E, Southgate, B, Bradley, L, Rus, S, Galvez-Cancino, F, McGivern, N, Güç, E, Kapourani, C-A, Byron, A, Ferguson, KM, Alfazema, N , Morrison, G , Grant, V , Blin, C, Sou, I, Marques-Torrejon, MA, Conde, L, Parrinello, S, Herrero, J, Beck, S, Brandner, S, Brennan, PM, Bertone, P, Pollard, JW, Quezada, SA, Sproul, D , Frame, MC , Serrels, A & Pollard, SM 2021, 'Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion', Cell. https://doi.org/10.1016/j.cell.2021.03.023

TY - JOUR

T1 - Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion

AU - Gangoso, Ester

AU - Southgate, Benjamin

AU - Bradley, Leanne

AU - Rus, Stefanie

AU - Galvez-Cancino, Felipe

AU - McGivern, Niamh

AU - Güç, Esra

AU - Kapourani, Chantriolnt-Andreas

AU - Byron, Adam

AU - Ferguson, Kirsty M

AU - Alfazema, Neza

AU - Morrison, Gillian

AU - Grant, Vivien

AU - Blin, Carla

AU - Sou, IengFong

AU - Marques-Torrejon, Maria Angeles

AU - Conde, Lucia

AU - Parrinello, Simona

AU - Herrero, Javier

AU - Beck, Stephan

AU - Brandner, Sebastian

AU - Brennan, Paul M

AU - Bertone, Paul

AU - Pollard, Jeffrey W

AU - Quezada, Sergio A

AU - Sproul, Duncan

AU - Frame, Margaret C

AU - Serrels, Alan

AU - Pollard, Steven M

PY - 2021/4/14

Y1 - 2021/4/14

N2 - 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.

AB - 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.

U2 - 10.1016/j.cell.2021.03.023

DO - 10.1016/j.cell.2021.03.023

M3 - Article

C2 - 33857425

SN - 0092-8674

JO - Cell

JF - Cell

ER -

Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion

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