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Human Mesenchymal g...
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Kaffes, IoannisEmory 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
(author)
Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors
- Article/chapterEnglish2019
Publisher, publication year, extent ...
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TAYLOR & FRANCIS INC,2019
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electronicrdacarrier
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LIBRIS-ID:oai:DiVA.org:uu-396107
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-396107URI
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https://doi.org/10.1080/2162402X.2019.1655360DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
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Szulzewsky, FrankFred Hutchinson Canc Res Ctr, Dept Human Biol, 1124 Columbia St, Seattle, WA 98104 USA
(author)
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Chen, ZhihongEmory 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
(author)
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Herting, Cameron J.Emory Univ, Aflac Canc & Blood Disorders Ctr, Childrens Healthcare Atlanta, Dept Pediat,Winship Canc Inst,Sch Med, Atlanta, GA USA
(author)
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Gabanic, BenEmory Univ, Aflac Canc & Blood Disorders Ctr, Childrens Healthcare Atlanta, Dept Pediat,Winship Canc Inst,Sch Med, Atlanta, GA USA
(author)
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Vega, Jose E. VelazquezEmory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
(author)
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Shelton, JenniferEmory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
(author)
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Switchenko, Jeffrey M.Emory Univ, Winship Canc Inst, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA
(author)
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Ross, James L.Emory Univ, Aflac Canc & Blood Disorders Ctr, Childrens Healthcare Atlanta, Dept Pediat,Winship Canc Inst,Sch Med, Atlanta, GA USA
(author)
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McSwain, Leon F.Emory Univ, Aflac Canc & Blood Disorders Ctr, Childrens Healthcare Atlanta, Dept Pediat,Winship Canc Inst,Sch Med, Atlanta, GA USA
(author)
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Huse, Jason T.Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA;Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
(author)
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Westermark, BengtUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)bengtwm
(author)
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Nelander, SvenUppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)svene843
(author)
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Forsberg Nilsson, Karin,1963-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)karifors
(author)
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Uhrbom, LeneUppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)leneuhrb
(author)
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Maturi, Naga PrathyushaUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)pnapr938
(author)
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Cimino, Patrick J.Fred Hutchinson Canc Res Ctr, Dept Human Biol, 1124 Columbia St, Seattle, WA 98104 USA;Univ Washington, Dept Pathol, Seattle, WA USA
(author)
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Holland, Eric C.Fred Hutchinson Canc Res Ctr, Dept Human Biol, 1124 Columbia St, Seattle, WA 98104 USA
(author)
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Kettenmann, HelmutMax Delbruck Ctr Mol Med, Dept Cellular Neurosci, Helmholtz Assoc, Berlin, Germany
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Brennan, Cameron W.Mem Sloan Kettering Canc Ctr, Dept Neurosurg, 1275 York Ave, New York, NY 10021 USA
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Brat, Daniel J.Northwestern Univ, Dept Pathol, Feinberg Sch Med, Ward Bldg Room 3-140,303 E Chicago Ave, Chicago, IL 60611 USA
(author)
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Hambardzumyan, DoloresEmory 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
(author)
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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, GermanyFred Hutchinson Canc Res Ctr, Dept Human Biol, 1124 Columbia St, Seattle, WA 98104 USA
(creator_code:org_t)
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In:Oncoimmunology: TAYLOR & FRANCIS INC8:112162-40112162-402X
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Kaffes, Ioannis
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Gabanic, Ben
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Shelton, Jennife ...
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Switchenko, Jeff ...
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Nelander, Sven
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Uhrbom, Lene
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Maturi, Naga Pra ...
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Holland, Eric C.
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