DNA methylation based glioblastoma subclassification is related to tumoral T-cell infiltration and patient survival

• Verfasst von: Dejaegher, Joost [VerfasserIn]
• Verfasst von: Solie, Lien [VerfasserIn]
• Verfasst von: Hunin, Zoé [VerfasserIn]
• Verfasst von: Sciot, Raf [VerfasserIn]
• Verfasst von: Capper, David [VerfasserIn]
• Verfasst von: Siewert, Christin [VerfasserIn]
• Verfasst von: Van Cauter, Sofie [VerfasserIn]
• Verfasst von: Wilms, Guido [VerfasserIn]
• Verfasst von: van Loon, Johan [VerfasserIn]
• Verfasst von: Ectors, Nadine [VerfasserIn]
• Verfasst von: Fieuws, Steffen [VerfasserIn]
• Verfasst von: Pfister, Stefan [VerfasserIn]
• Verfasst von: Van Gool, Stefaan W [VerfasserIn]
• Verfasst von: De Vleeschouwer, Steven [VerfasserIn]
• Titel: DNA methylation based glioblastoma subclassification is related to tumoral T-cell infiltration and patient survival
• Verf.angabe: Joost Dejaegher, Lien Solie, Zoé Hunin, Raf Sciot, David Capper, Christin Siewert, Sofie Van Cauter, Guido Wilms, Johan van Loon, Nadine Ectors, Steffen Fieuws, Stefan M. Pfister, Stefaan W. Van Gool, and Steven De Vleeschouwer
• Jahr: 2021
• Jahr des Originals: 2020
• Umfang: 11 S.
• Teil: volume:23
• Teil: year:2021
• Teil: number:2
• Teil: month:02
• Teil: pages:240-250
• Teil: extent:11
• Fussnoten: Gesehen am 10.06.2021 ; First published: 01 November 2020
• Titel Quelle: Enthalten in: Neuro-Oncology
• Ort Quelle: Oxford : Oxford Univ. Press, 1999
• Jahr Quelle: 2021
• Band/Heft Quelle: 23(2021), 2 vom: Feb., Seite 240-250
• ISSN Quelle: 1523-5866
• DOI: doi:10.1093/neuonc/noaa247
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1760248401

Abstract

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 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.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).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.