The Cancer Stem Cell Subtype Determines Immune Infiltration of Glioblastoma

被引：64

作者：

Beier, Christoph P. ^{[1
,2
,3
]}

Kumar, Praveen ^{[1
,2
,3
,4
]}

Meyer, Katharina ^{[5
]}

Leukel, Petra ^{[4
]}

Bruttel, Valentin ^{[6
,7
]}

Aschenbrenner, Ines ^{[4
]}

Riemenschneider, Markus J. ^{[8
]}

Fragoulis, Athanassios ^{[9
]}

Ruemmele, Petra ^{[10
]}

Lamszus, Katrin ^{[11
]}

Schulz, Joerg B. ^{[1
,2
,3
]}

Weis, Joachim ^{[2
,3
,12
]}

Bogdahn, Ulrich ^{[4
]}

Wischhusen, Joerg ^{[6
,7
]}

Hau, Peter ^{[4
]}

Spang, Rainer ^{[5
]}

Beier, Dagmar ^{[1
,2
,3
]}

机构：

[1] Rhein Westfal TH Aachen, Dept Neurol, D-52074 Aachen, Germany

[2] JARA Translat Brain Med, Aachen, Germany

[3] JARA Translat Brain Med, Julich, Germany

[4] Univ Regensburg, Sch Med, Dept Neurol, Regensburg, Germany

[5] Univ Regensburg, Sch Med, Inst Funct Genom, Computat Diagnost Grp, Regensburg, Germany

[6] Univ Wurzburg, Interdisciplinary Ctr Clin Res, Jr Res Grp Tumor Progress & Immune Escape, Wurzburg, Germany

[7] Dept Gynecol & Obstet, Wurzburg, Germany

[8] Regensburg Univ Hosp, Dept Neuropathol, Regensburg, Germany

[9] Rhein Westfal TH Aachen, Inst Anat & Cellular Biol, D-52062 Aachen, Germany

[10] Univ Regensburg, Sch Med, Dept Pathol, Regensburg, Germany

[11] Univ Hamburg Hosp, Sch Med, Dept Neurosurg, D-2000 Hamburg, Germany

[12] Rhein Westfal TH Aachen, Dept Neuropathol, D-52074 Aachen, Germany

来源：

STEM CELLS AND DEVELOPMENT | 2012年 / 21卷 / 15期

关键词：

TGF-BETA; SELF-RENEWAL; GLIOMA-CELLS; IN-VIVO; GROWTH; EXPRESSION; PROFILES; LINES; INVASIVENESS; SUBCLASSES;

D O I：

10.1089/scd.2011.0660

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：2753 / 2761

页数：9

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