Inhibition of Colony-Stimulating Factor-1 Receptor Enhances the Efficacy of Radiotherapy and Reduces Immune Suppression in Glioblastoma.
AIM: To use inhibition of colony-stimulating factor-1 receptor (CSF-1R) to target tumor-associated macrophages (TAMs) and improve the efficacy of radiotherapy in glioblastoma (GBM).
MATERIALS AND METHODS: The CSF-1R inhibitor BLZ-945 was used to examine the impact of CSF-1R inhibition on M2 polarization in vitro. Using an orthotopic, immunocompetent GBM model, mice were treated with vehicle, RT, BLZ-945, or RT plus BLZ-945.
RESULTS: BLZ-945 reduced M2 polarization in vitro. BLZ-945 alone did not improve median overall survival (mOS=29 days) compared to control mice (mOS=27 days). RT improved survival (mOS=45 days; p=0.02), while RT plus BLZ-945 led to the longest survival (mOS=not reached; p=0.005). Resected tumors had a relatively large population of M2 TAMs in GBM at baseline, which was increased in response to RT. BLZ-945 reduced RT-induced M2 infiltration.
CONCLUSION: Inhibition of CSF-1R improved response to RT in the treatment of GBM and may represent a promising strategy to improve RT-induced antitumor immune responses.
Almahariq MF, Quinn TJ, Kesarwani P, Kant S, Miller CR, Chinnaiyan P. Inhibition of Colony-Stimulating Factor-1 Receptor Enhances the Efficacy of Radiotherapy and Reduces Immune Suppression in Glioblastoma. In Vivo. 2021 Jan-Feb;35(1):119-129. doi: 10.21873/invivo.12239. PMID: 33402457; PMCID: PMC7880776.