英国爱丁堡大学Steven M. Pollard研究团队发现，胶质母细胞瘤通过表观遗传学免疫编辑获得髓样相关的转录程序，从而引发免疫逃避 。这一研究成果于2021年4月14日在线发表在国际学术期刊《细胞》上。
研究人员探讨了多形胶质母细胞瘤（GBM）中免疫逃逸的潜在机制。通过将GBM干细胞（GSC）连续移植到具有免疫能力的宿主中，研究人员发现了通过建立增强的免疫抑制肿瘤微环境而获得的GSC免疫逃避能力。从机制上讲，这不是通过肿瘤亚克隆的遗传选择引起的，而是表观遗传学的免疫编辑过程，在免疫攻击后，GSC的稳定转录和表观遗传学变化被强制执行。这些变化启动了髓细胞相关的转录程序，从而导致与肿瘤相关巨噬细胞招募的增加。
此外，研究人员在人类间充质亚型GSC中发现相似的表观遗传学和转录特征。研究人员认为，通过重塑肿瘤免疫微环境，表观遗传免疫编辑可能会在最具攻击性的间质性GBM亚型中驱动获得性免疫逃逸程序。
据悉，GBM是一种侵袭性脑肿瘤，目前的免疫治疗方法尚未成功。
附：英文原文
Title: Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion
Author: Ester Gangoso, Benjamin Southgate, Leanne Bradley, Stefanie Rus, Felipe Galvez-Cancino, Niamh McGivern, Esra Gü, 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
Issue&Volume: 2021-04-14
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.
DOI: 10.1016/j.cell.2021.03.023
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00351-2