PT  - JOURNAL ARTICLE
AU  - ALMAHARIQ, MUAYAD F.
AU  - QUINN, THOMAS J.
AU  - KESARWANI, PRAVIN
AU  - KANT, SHIVA
AU  - MILLER, C. RYAN
AU  - CHINNAIYAN, PRAKASH
TI  - Inhibition of Colony-Stimulating Factor-1 Receptor Enhances the Efficacy of Radiotherapy and Reduces Immune Suppression in Glioblastoma
AID  - 10.21873/invivo.12239
DP  - 2021 Jan 01
TA  - In Vivo
PG  - 119--129
VI  - 35
IP  - 1
4099  - http://iv.iiarjournals.org/content/35/1/119.short
4100  - http://iv.iiarjournals.org/content/35/1/119.full
SO  - In Vivo2021 Jan 01; 35
AB  - 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.