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Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors
Emory Univ, Aflac Canc & Blood Disorders Ctr, Childrens Healthcare Atlanta, Dept Pediat,Winship Canc Inst,Sch Med, Atlanta, GA USA;Max Delbruck Ctr Mol Med, Dept Cellular Neurosci, Helmholtz Assoc, Berlin, Germany.
Fred Hutchinson Canc Res Ctr, Dept Human Biol, 1124 Columbia St, Seattle, WA 98104 USA.
Emory Univ, Aflac Canc & Blood Disorders Ctr, Childrens Healthcare Atlanta, Dept Pediat,Winship Canc Inst,Sch Med, Atlanta, GA USA;Emory Univ, Winship Canc Inst, Discovery & Dev Therapeut Program, Atlanta, GA 30322 USA.ORCID iD: 0000-0001-7403-7015
Emory Univ, Aflac Canc & Blood Disorders Ctr, Childrens Healthcare Atlanta, Dept Pediat,Winship Canc Inst,Sch Med, Atlanta, GA USA.
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2019 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 8, no 11Article in journal (Refereed) Published
Abstract [en]

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding of pathogenetic mechanisms and patient stratification. Concurrently, the role of immune cells in the tumor microenvironment has received increasing attention, especially T cells and tumor-associated macrophages (TAM). The latter are a mixed population of activated brain-resident microglia and infiltrating monocytes/monocyte-derived macrophages, both of which express ionized calcium-binding adapter molecule 1 (IBA1). This study investigated differences in immune cell subpopulations among distinct transcriptional subtypes of GBM. Human GBM samples were molecularly characterized and assigned to Proneural, Mesenchymal or Classical subtypes as defined by NanoString nCounter Technology. Subsequently, we performed and analyzed automated immunohistochemical stainings for TAM as well as specific T cell populations. The Mesenchymal subtype of GBM showed the highest presence of TAM, CD8(+), CD3(+) and FOXP3(+) T cells, as compared to Proneural and Classical subtypes. High expression levels of the TAM-related gene AIF1, which encodes the TAM-specific protein IBA1, correlated with a worse prognosis in Proneural GBM, but conferred a survival benefit in Mesenchymal tumors. We used our data to construct a mathematical model that could reliably identify Mesenchymal GBM with high sensitivity using a combination of the aforementioned cell-specific IHC markers. In conclusion, we demonstrated that molecularly distinct GBM subtypes are characterized by profound differences in the composition of their immune microenvironment, which could potentially help to identify tumors amenable to immunotherapy.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS INC , 2019. Vol. 8, no 11
Keywords [en]
Glioblastoma, microenvironment, subtype, macrophage, T cell, AIF1
National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-396107DOI: 10.1080/2162402X.2019.1655360ISI: 000483119600001PubMedID: 31646100OAI: oai:DiVA.org:uu-396107DiVA, id: diva2:1367144
Funder
Swedish Cancer Society, 110363Swedish Cancer Society, 140385Swedish Cancer Society, 130500Swedish Research Council, 521-2013-3356German Research Foundation (DFG), SZ 350/1-1Available from: 2019-11-01 Created: 2019-11-01 Last updated: 2019-11-01Bibliographically approved

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