Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance.

Details

Serval ID
serval:BIB_1B0920FD434E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance.
Journal
Science Translational Medicine
Author(s)
Akkari L., Bowman R.L., Tessier J., Klemm F., Handgraaf S.M., de Groot M., Quail D.F., Tillard L., Gadiot J., Huse J.T., Brandsma D., Westerga J., Watts C., Joyce J.A.
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
15/07/2020
Peer-reviewed
Oui
Volume
12
Number
552
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Tumor-associated macrophages (TAMs) and microglia (MG) are potent regulators of glioma development and progression. However, the dynamic alterations of distinct TAM populations during the course of therapeutic intervention, response, and recurrence have not yet been fully explored. Here, we investigated how radiotherapy changes the relative abundance and phenotypes of brain-resident MG and peripherally recruited monocyte-derived macrophages (MDMs) in glioblastoma. We identified radiation-specific, stage-dependent MG and MDM gene expression signatures in murine gliomas and confirmed altered expression of several genes and proteins in recurrent human glioblastoma. We found that targeting these TAM populations using a colony-stimulating factor-1 receptor (CSF-1R) inhibitor combined with radiotherapy substantially enhanced survival in preclinical models. Our findings reveal the dynamics and plasticity of distinct macrophage populations in the irradiated tumor microenvironment, which has translational relevance for enhancing the efficacy of standard-of-care treatment in gliomas.
Pubmed
Create date
24/07/2020 14:13
Last modification date
10/09/2020 5:26
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