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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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

Fingeraftryk

Glioblastoma
Cell Line

Citer dette

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. / The cancer stem cell subtype determines immune infiltration of glioblastoma. I: Stem Cells and Development. 2012 ; Bind 21, Nr. 15. s. 2753-61.
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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.",
keywords = "Animals, Brain Neoplasms/immunology, Cell Line, Tumor, Cell Proliferation, Gene Expression Regulation, Neoplastic, Glioblastoma/immunology, Humans, Immunologic Factors/physiology, Mice, NK Cell Lectin-Like Receptor Subfamily K/genetics, Neoplasm Transplantation, Neoplastic Stem Cells/immunology, Oligonucleotide Array Sequence Analysis, Phosphorylation, Protein Processing, Post-Translational, Smad2 Protein/metabolism, T-Lymphocytes, Cytotoxic/immunology, Transcriptional Activation, Transcriptome, Transforming Growth Factor beta/physiology, Tumor Burden/immunology",
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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month = "10",
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language = "English",
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journal = "Stem Cells and Development",
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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, bind 21, nr. 15, s. 2753-61. https://doi.org/10.1089/scd.2011.0660

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.

I: Stem Cells and Development, Bind 21, Nr. 15, 10.10.2012, s. 2753-61.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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/immunology

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Gene Expression Regulation, Neoplastic

KW - Glioblastoma/immunology

KW - Humans

KW - Immunologic Factors/physiology

KW - Mice

KW - NK Cell Lectin-Like Receptor Subfamily K/genetics

KW - Neoplasm Transplantation

KW - Neoplastic Stem Cells/immunology

KW - Oligonucleotide Array Sequence Analysis

KW - Phosphorylation

KW - Protein Processing, Post-Translational

KW - Smad2 Protein/metabolism

KW - T-Lymphocytes, Cytotoxic/immunology

KW - Transcriptional Activation

KW - Transcriptome

KW - Transforming Growth Factor beta/physiology

KW - Tumor Burden/immunology

U2 - 10.1089/scd.2011.0660

DO - 10.1089/scd.2011.0660

M3 - Journal article

VL - 21

SP - 2753

EP - 2761

JO - Stem Cells and Development

JF - Stem Cells and Development

SN - 1547-3287

IS - 15

ER -