The cancer stem cell subtype determines immune infiltration of glioblastoma

Christoph P Beier, Praveen Kumar, Katharina Meyer, Petra Leukel, Valentin Bruttel, Ines Aschenbrenner, Markus J Riemenschneider, Athanassios Fragoulis, Petra Rümmele, Katrin Lamszus, Jörg B Schulz, Joachim Weis, Ulrich Bogdahn, Jörg Wischhusen, Peter Hau, Rainer Spang, Dagmar Beier

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Abstrakt

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.

OriginalsprogEngelsk
TidsskriftStem Cells and Development
Vol/bind21
Udgave nummer15
Sider (fra-til)2753-61
Antal sider9
ISSN1547-3287
DOI
StatusUdgivet - 10. okt. 2012
Udgivet eksterntJa

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