| First Author | Watson SS | Year | 2024 |
| Journal | Cancer Cell | Volume | 42 |
| Issue | 9 | Pages | 1507-1527.e11 |
| PubMed ID | 39255775 | Mgi Jnum | J:358824 |
| Mgi Id | MGI:7719665 | Doi | 10.1016/j.ccell.2024.08.012 |
| Citation | Watson SS, et al. (2024) Fibrotic response to anti-CSF-1R therapy potentiates glioblastoma recurrence. Cancer Cell 42(9):1507-1527.e11 |
| abstractText | 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 approximately 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 beta (TGF-beta) 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. |
