期刊
STEM CELLS AND DEVELOPMENT
卷 21, 期 15, 页码 2753-2761出版社
MARY ANN LIEBERT INC
DOI: 10.1089/scd.2011.0660
关键词
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资金
- Bavarian Research Foundation
- BayGene
- NGFNplus Brain Tumor Network
- Subproject 7A and 7B [01GS0887, 01GS1105]
- RWTH Aachen, Medical School (START-Program)
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.
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