Details

Autor(en) / Beteiligte

• Henrik Heiland, Dieter
• Ravi, Vidhya M
• Behringer, Simon P
• Frenking, Jan Hendrik
• Wurm, Julian
• Joseph, Kevin
• Garrelfs, Nicklas W C
• Strähle, Jakob
• Heynckes, Sabrina
• Grauvogel, Jürgen
• Franco, Pamela
• Mader, Irina
• Schneider, Matthias
• Potthoff, Anna-Laura
• Delev, Daniel
• Hofmann, Ulrich G
• Fung, Christian
• Beck, Jürgen
• Sankowski, Roman
• Prinz, Marco
• Schnell, Oliver

Titel

Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma

Ist Teil von

• Nature communications, 2019-06, Vol.10 (1), p.2541-2541, Article 2541

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Reactive astrocytes evolve after brain injury, inflammatory and degenerative diseases, whereby they undergo transcriptomic re-programming. In malignant brain tumors, their function and crosstalk to other components of the environment is poorly understood. Here we report a distinct transcriptional phenotype of reactive astrocytes from glioblastoma linked to JAK/STAT pathway activation. Subsequently, we investigate the origin of astrocytic transformation by a microglia loss-of-function model in a human organotypic slice model with injected tumor cells. RNA-seq based gene expression analysis of astrocytes reveals a distinct astrocytic phenotype caused by the coexistence of microglia and astrocytes in the tumor environment, which leads to a large release of anti-inflammatory cytokines such as TGFβ, IL10 and G-CSF. Inhibition of the JAK/STAT pathway shifts the balance of pro- and anti-inflammatory cytokines towards a pro-inflammatory environment. The complex interaction of astrocytes and microglia cells promotes an immunosuppressive environment, suggesting that tumor-associated astrocytes contribute to anti-inflammatory responses.