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

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2753-2761
Number of pages9
JournalStem Cells and Development
Volume21
Issue number15
DOIs
Publication statusPublished - 10-10-2012

All Science Journal Classification (ASJC) codes

  • Hematology
  • Developmental Biology
  • Cell Biology

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