Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance Journal Article
| Authors: | 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. |
| Article Title: | Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance |
| 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. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. |
| Journal Title: | Science Translational Medicine |
| Volume: | 12 |
| Issue: | 552 |
| ISSN: | 1946-6234 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2020-07-15 |
| Start Page: | eaaw7843 |
| Language: | English |
| DOI: | 10.1126/scitranslmed.aaw7843 |
| PUBMED: | 32669424 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work