Dejaegher, Joost, Solie, Lien, Hunin, Zoe, Sciot, Raf, Capper, David ORCID: 0000-0003-1945-497X, Siewert, Christin, Van Cauter, Sofie, Wilms, Guido, van Loon, Johan, Ectors, Nadine, Fieuws, Steffen, Pfister, Stefan M., Van Gool, Stefaan W. and De Vleeschouwer, Steven (2021). DNA methylation based glioblastoma subclassification is related to tumoral T-cell infiltration and patient survival. Neuro-Oncology, 23 (2). S. 240 - 251. CARY: OXFORD UNIV PRESS INC. ISSN 1523-5866

Full text not available from this repository.

Abstract

Background. 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. Methods. 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 Programmed cell death protein 1 (PD-1) expression were evaluated. Circulating immune cell populations and selected cytokines were assessed on blood samples taken before and after radiochemotherapy. Results. Forty-two tumors had a mesenchymal, 27 a receptor tyrosine kinase (RTK) II, 17 RTK I, and 7 an isocitrate dehydrogenase (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 mo), intermediate in RTK II tumors (27 mo), and significantly lower in mesenchymal and RTK I groups (15.5 and 16 mo, respectively). Conclusions. 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dejaegher, JoostUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Solie, LienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunin, ZoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sciot, RafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Capper, DavidUNSPECIFIEDorcid.org/0000-0003-1945-497XUNSPECIFIED
Siewert, ChristinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Cauter, SofieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wilms, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Loon, JohanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ectors, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fieuws, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfister, Stefan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Gool, Stefaan W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Vleeschouwer, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-601952
DOI: 10.1093/neuonc/noaa247
Journal or Publication Title: Neuro-Oncology
Volume: 23
Number: 2
Page Range: S. 240 - 251
Date: 2021
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 1523-5866
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Oncology; Clinical NeurologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60195

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item