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