CSF-1R inhibition alters macrophage polarization and blocks glioma progression Journal Article

Authors: Pyonteck, S. M.; Akkari, L.; Schuhmacher, A. J.; Bowman, R. L.; Sevenich, L.; Quail, D. F.; Olson, O. C.; Quick, M. L.; Huse, J. T.; Teijeiro, V.; Setty, M.; Leslie, C. S.; Oei, Y.; Pedraza, A.; Zhang, J.; Brennan, C. W.; Sutton, J. C.; Holland, E. C.; Daniel, D.; Joyce, J. A.
Article Title: CSF-1R inhibition alters macrophage polarization and blocks glioma progression
Abstract: Glioblastoma multiforme (GBM) comprises several molecular subtypes, including proneural GBM. Most therapeutic approaches targeting glioma cells have failed. An alternative strategy is to target cells in the glioma microenvironment, such as tumor-associated macrophages and microglia (TAMs). Macrophages depend on colony stimulating factor-1 (CSF-1) for differentiation and survival. We used an inhibitor of the CSF-1 receptor (CSF-1R) to target TAMs in a mouse proneural GBM model, which significantly increased survival and regressed established tumors. CSF-1R blockade additionally slowed intracranial growth of patient-derived glioma xenografts. Surprisingly, TAMs were not depleted in treated mice. Instead, glioma-secreted factors, including granulocyte-macrophage CSF (GM-CSF) and interferon-γ (IFN-γ), facilitated TAM survival in the context of CSF-1R inhibition. Expression of alternatively activated M2 markers decreased in surviving TAMs, which is consistent with impaired tumor-promoting functions. These gene signatures were associated with enhanced survival in patients with proneural GBM. Our results identify TAMs as a promising therapeutic target for proneural gliomas and establish the translational potential of CSF-1R inhibition for GBM. © 2013 Nature America, Inc. All rights reserved.
Journal Title: Nature Medicine
Volume: 19
Issue: 10
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2013-10-01
Start Page: 1264
End Page: 1272
Language: English
DOI: 10.1038/nm.3337
PROVIDER: scopus
PMCID: PMC3840724
PUBMED: 24056773
Notes: --- - Cited By (since 1996):2 - "Export Date: 2 December 2013" - "CODEN: NAMEF" - "Source: Scopus"
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MSK Authors
  1. Cameron Brennan
    156 Brennan
  2. Eric Holland
    219 Holland
  3. Jason T Huse
    127 Huse
  4. Johanna A Joyce
    67 Joyce
  5. Alicia Maria Pedraza
    20 Pedraza
  6. Christina Leslie
    111 Leslie
  7. Leila Akkari
    15 Akkari
  8. Manu Setty
    22 Setty
  9. Robert L Bowman
    22 Bowman
  10. Oakley Christopher Olson
    12 Olson
  11. Stephanie Harris
    4 Harris
  12. Daniela Francis Quail
    12 Quail
  13. Marsha Lee Quick
    8 Quick
  14. Jianan Zhang
    7 Zhang