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

doi:10.1089/scd.2011.0660

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

Department of Biotechnology, Manipal Institute of Technology, Manipal

Research output: Contribution to journal › Article › peer-review

54 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 language	English
Pages (from-to)	2753-2761
Number of pages	9
Journal	Stem Cells and Development
Volume	21
Issue number	15
DOIs	https://doi.org/10.1089/scd.2011.0660
Publication status	Published - 10-10-2012

All Science Journal Classification (ASJC) codes

Hematology
Developmental Biology
Cell Biology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1089/scd.2011.0660

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Beier, C. P., Kumar, P., Meyer, K., Leukel, P., Bruttel, V., Aschenbrenner, I., Riemenschneider, M. J., Fragoulis, A., Rümmele, P., Lamszus, K., Schulz, J. B., Weis, J., Bogdahn, U., Wischhusen, J., Hau, P., Spang, R., & Beier, D. (2012). The cancer stem cell subtype determines immune infiltration of Glioblastoma. Stem Cells and Development, 21(15), 2753-2761. https://doi.org/10.1089/scd.2011.0660

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title = "The cancer stem cell subtype determines immune infiltration of Glioblastoma",

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.",

author = "Beier, {Christoph P.} and Praveen Kumar and Katharina Meyer and Petra Leukel and Valentin Bruttel and Ines Aschenbrenner and Riemenschneider, {Markus J.} and Athanassios Fragoulis and Petra R{\"u}mmele and Katrin Lamszus and Schulz, {J{\"o}rg B.} and Joachim Weis and Ulrich Bogdahn and J{\"o}rg Wischhusen and Peter Hau and Rainer Spang and Dagmar Beier",

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Beier, CP, Kumar, P, Meyer, K, Leukel, P, Bruttel, V, Aschenbrenner, I, Riemenschneider, MJ, Fragoulis, A, Rümmele, P, Lamszus, K, Schulz, JB, Weis, J, Bogdahn, U, Wischhusen, J, Hau, P, Spang, R & Beier, D 2012, 'The cancer stem cell subtype determines immune infiltration of Glioblastoma', Stem Cells and Development, vol. 21, no. 15, pp. 2753-2761. https://doi.org/10.1089/scd.2011.0660

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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.

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The cancer stem cell subtype determines immune infiltration of Glioblastoma

Abstract

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