%0 Journal Article
%A Dejaegher, Joost
%A Solie, Lien
%A Hunin, Zoé
%A Sciot, Raf
%A Capper, David
%A Siewert, Christin
%A Van Cauter, Sofie
%A Wilms, Guido
%A van Loon, Johan
%A Ectors, Nadine
%A Fieuws, Steffen
%A Pfister, Stefan
%A Van Gool, Stefaan W
%A De Vleeschouwer, Steven
%T DNA Methylation based glioblastoma subclassification is related to tumoral T cell infiltration and patient survival.
%J Neuro-Oncology
%V 23
%N 2
%@ 1523-5866
%C Oxford
%I Oxford Univ. Press
%M DKFZ-2020-02380
%P 240-250
%D 2021
%Z 2021 Feb 25;23(2):240-250
%X Histologically classified Glioblastomas (GBM) can have different clinical behavior and response to therapy, for which molecular subclassifications have been proposed. We evaluated the relationship of epigenetic GBM subgroups with immune cell infiltrations, systemic immune changes during radiochemotherapy and clinical outcome.450K genome-wide DNA methylation was assessed on tumor tissue from 93 patients with newly diagnosed GBM, treated with standard radiochemotherapy and experimental immunotherapy. Tumor infiltration of T cells, myeloid cells and PD-1 expression were evaluated. Circulating immune cell populations and selected cytokines were assessed on blood samples taken before and after radiochemotherapy.Forty-two tumors had a mesenchymal, 27 a RTK II, 17 a RTK I and 7 an IDH DNA methylation pattern Mesenchymal tumors had the highest amount of tumor-infiltrating CD3+ and CD8+ T cells and IDH tumors the lowest. There were no significant differences for CD68+ cells, FoxP3+ cells and PD-1 expression between groups. Systemically, there was a relative increase of CD8+ T cells and CD8+ PD-1 expression and a relative decrease of CD4+ T cells after radiochemotherapy in all subgroups except IDH tumors. Overall survival was the longest in the IDH group (median 36 months), intermediate in RTK II tumors (27 months) and significantly lower in mesenchymal and RTK I groups (15.5 and 16 months respectively).Methylation based stratification of GBM is related to T cell infiltration and survival, with IDH and mesenchymal tumors representing both ends of a spectrum. DNA methylation profiles could be useful in stratifying patients for immunotherapy trials.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33130898
%R 10.1093/neuonc/noaa247
%U https://inrepo02.dkfz.de/record/164297