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Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors

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Item Type:Article
Title:Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors
Creators Name:Kaffes, I. and Szulzewsky, F. and Chen, Z. and Herting, C.J. and Gabanic, B. and Velázquez Vega, J.E. and Shelton, J. and Switchenko, J.M. and Ross, J.L. and McSwain, L.F. and Huse, J.T. and Westermark, B. and Nelander, S. and Forsberg-Nilsson, K. and Uhrbom, L. and Maturi, N.P. and Cimino, P.J. and Holland, E.C. and Kettenmann, H. and Brennan, C.W. and Brat, D.J. and Hambardzumyan, D.
Abstract: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.
Keywords:Glioblastoma, Microenvironment, Subtype, Macrophage, T Cell, AIF1
Publisher:Taylor & Francis
Page Range:e1655360
Date:22 August 2019
Official Publication:https://doi.org/10.1080/2162402X.2019.1655360
PubMed:View item in PubMed

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