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

Heiland DH, Ravi VM, Behringer SP, Frenking JH, Wurm J, Joseph K, Garrelfs NW, Strähle J, Heynckes S, Grauvogel J, Franco P, Mader I, Schneider M, Potthoff AL, Delev D, Hofmann UG, Fung C, Beck J, Sankowski R, Prinz M, Schnell O (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 10

Article Number: 2541

Journal Issue: 1

DOI: 10.1038/s41467-019-10493-6

Abstract

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.

Authors with CRIS profile

Dieter Henrik Heiland
Oliver Schnell

Involved external institutions

Universitätsklinikum Freiburg DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Universitätsklinikum Aachen (UKA) DE Germany (DE)

How to cite

APA:

Heiland, D.H., Ravi, V.M., Behringer, S.P., Frenking, J.H., Wurm, J., Joseph, K.,... Schnell, O. (2019). Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-10493-6

MLA:

Heiland, Dieter Henrik, et al. "Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma." Nature Communications 10.1 (2019).

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