RT Journal Article
SR Electronic
T1 Inhibition of Colony-Stimulating Factor-1 Receptor Enhances the Efficacy of Radiotherapy and Reduces Immune Suppression in Glioblastoma
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 119
OP 129
DO 10.21873/invivo.12239
VO 35
IS 1
A1 MUAYAD F. ALMAHARIQ
A1 THOMAS J. QUINN
A1 PRAVIN KESARWANI
A1 SHIVA KANT
A1 C. RYAN MILLER
A1 PRAKASH CHINNAIYAN
YR 2021
UL http://iv.iiarjournals.org/content/35/1/119.abstract
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.