TY  - JOUR
AU  - Dejaegher, Joost
AU  - Solie, Lien
AU  - Hunin, Zoé
AU  - Sciot, Raf
AU  - Capper, David
AU  - Siewert, Christin
AU  - Van Cauter, Sofie
AU  - Wilms, Guido
AU  - van Loon, Johan
AU  - Ectors, Nadine
AU  - Fieuws, Steffen
AU  - Pfister, Stefan
AU  - Van Gool, Stefaan W
AU  - De Vleeschouwer, Steven
TI  - DNA Methylation based glioblastoma subclassification is related to tumoral T cell infiltration and patient survival.
JO  - Neuro-Oncology
VL  - 23
IS  - 2
SN  - 1523-5866
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2020-02380
SP  - 240-250
PY  - 2021
N1  - 2021 Feb 25;23(2):240-250
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:33130898
DO  - DOI:10.1093/neuonc/noaa247
UR  - https://inrepo02.dkfz.de/record/164297
ER  -