Fibrotic response to anti-CSF-1R therapy potentiates glioblastoma recurrence.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_ACA88D313315
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fibrotic response to anti-CSF-1R therapy potentiates glioblastoma recurrence.
Journal
Cancer cell
Author(s)
Watson S.S., Zomer A., Fournier N., Lourenco J., Quadroni M., Chryplewicz A., Nassiri S., Aubel P., Avanthay S., Croci D., Abels E., Broekman MLD, Hanahan D., Huse J.T., Daniel R.T., Hegi M.E., Homicsko K., Cossu G., Hottinger A.F., Joyce J.A.
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Publication state
Published
Issued date
09/09/2024
Peer-reviewed
Oui
Volume
42
Number
9
Pages
1507-1527.e11
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Glioblastoma recurrence is currently inevitable despite extensive standard-of-care treatment. In preclinical studies, an alternative strategy of targeting tumor-associated macrophages and microglia through CSF-1R inhibition was previously found to regress established tumors and significantly increase overall survival. However, recurrences developed in ∼50% of mice in long-term studies, which were consistently associated with fibrotic scars. This fibrotic response is observed following multiple anti-glioma therapies in different preclinical models herein and in patient recurrence samples. Multi-omics analyses of the post-treatment tumor microenvironment identified fibrotic areas as pro-tumor survival niches that encapsulated surviving glioma cells, promoted dormancy, and inhibited immune surveillance. The fibrotic treatment response was mediated by perivascular-derived fibroblast-like cells via activation by transforming growth factor β (TGF-β) signaling and neuroinflammation. Concordantly, combinatorial inhibition of these pathways inhibited treatment-associated fibrosis, and significantly improved survival in preclinical trials of anti-colony-stimulating factor-1 receptor (CSF-1R) therapy.
Keywords
Glioblastoma/drug therapy, Glioblastoma/pathology, Animals, Humans, Mice, Neoplasm Recurrence, Local/drug therapy, Neoplasm Recurrence, Local/pathology, Tumor Microenvironment/drug effects, Fibrosis, Brain Neoplasms/drug therapy, Brain Neoplasms/pathology, Receptor, Macrophage Colony-Stimulating Factor/antagonists & inhibitors, Receptor, Macrophage Colony-Stimulating Factor/metabolism, Cell Line, Tumor, Signal Transduction/drug effects, Xenograft Model Antitumor Assays, Transforming Growth Factor beta/metabolism
Pubmed
Open Access
Yes
Create date
13/09/2024 15:48
Last modification date
14/09/2024 7:12
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