The cancer stem cell subtype determines immune infiltration of glioblastoma
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The cancer stem cell subtype determines immune infiltration of glioblastoma. / Beier, Christoph P; Kumar, Praveen; Meyer, Katharina; Leukel, Petra; Bruttel, Valentin; Aschenbrenner, Ines; Riemenschneider, Markus J; Fragoulis, Athanassios; Rümmele, Petra; Lamszus, Katrin; Schulz, Jörg B; Weis, Joachim; Bogdahn, Ulrich; Wischhusen, Jörg; Hau, Peter; Spang, Rainer; Beier, Dagmar.
in: STEM CELLS DEV, Jahrgang 21, Nr. 15, 10.10.2012, S. 2753-61.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The cancer stem cell subtype determines immune infiltration of glioblastoma
AU - Beier, Christoph P
AU - Kumar, Praveen
AU - Meyer, Katharina
AU - Leukel, Petra
AU - Bruttel, Valentin
AU - Aschenbrenner, Ines
AU - Riemenschneider, Markus J
AU - Fragoulis, Athanassios
AU - Rümmele, Petra
AU - Lamszus, Katrin
AU - Schulz, Jörg B
AU - Weis, Joachim
AU - Bogdahn, Ulrich
AU - Wischhusen, Jörg
AU - Hau, Peter
AU - Spang, Rainer
AU - Beier, Dagmar
PY - 2012/10/10
Y1 - 2012/10/10
N2 - Immune cell infiltration varies widely between different glioblastomas (GBMs). The underlying mechanism, however, remains unknown. Here we show that TGF-beta regulates proliferation, migration, and tumorigenicity of mesenchymal GBM cancer stem cells (CSCs) in vivo and in vitro. In contrast, proneural GBM CSCs resisted TGF-beta due to TGFR2 deficiency. In vivo, a substantially increased infiltration of immune cells was observed in mesenchymal GBMs, while immune infiltrates were rare in proneural GBMs. On a functional level, proneural CSC lines caused a significantly stronger TGF-beta-dependent suppression of NKG2D expression on CD8(+) T and NK cells in vitro providing a mechanistic explanation for the reduced immune infiltration of proneural GBMs. Thus, the molecular subtype of CSCs TGF-beta-dependently contributes to the degree of immune infiltration.
AB - Immune cell infiltration varies widely between different glioblastomas (GBMs). The underlying mechanism, however, remains unknown. Here we show that TGF-beta regulates proliferation, migration, and tumorigenicity of mesenchymal GBM cancer stem cells (CSCs) in vivo and in vitro. In contrast, proneural GBM CSCs resisted TGF-beta due to TGFR2 deficiency. In vivo, a substantially increased infiltration of immune cells was observed in mesenchymal GBMs, while immune infiltrates were rare in proneural GBMs. On a functional level, proneural CSC lines caused a significantly stronger TGF-beta-dependent suppression of NKG2D expression on CD8(+) T and NK cells in vitro providing a mechanistic explanation for the reduced immune infiltration of proneural GBMs. Thus, the molecular subtype of CSCs TGF-beta-dependently contributes to the degree of immune infiltration.
KW - Animals
KW - Brain Neoplasms
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Gene Expression Regulation, Neoplastic
KW - Glioblastoma
KW - Humans
KW - Immunologic Factors
KW - Mice
KW - NK Cell Lectin-Like Receptor Subfamily K
KW - Neoplasm Transplantation
KW - Neoplastic Stem Cells
KW - Oligonucleotide Array Sequence Analysis
KW - Phosphorylation
KW - Protein Processing, Post-Translational
KW - Smad2 Protein
KW - T-Lymphocytes, Cytotoxic
KW - Transcriptional Activation
KW - Transcriptome
KW - Transforming Growth Factor beta
KW - Tumor Burden
U2 - 10.1089/scd.2011.0660
DO - 10.1089/scd.2011.0660
M3 - SCORING: Journal article
C2 - 22676416
VL - 21
SP - 2753
EP - 2761
JO - STEM CELLS DEV
JF - STEM CELLS DEV
SN - 1547-3287
IS - 15
ER -