The study investigates the therapeutic potential of colony-stimulating factor-1 receptor (CSF-1R) inhibition in glioblastoma multiforme (GBM), a highly aggressive form of brain cancer. CSF-1R inhibition was found to significantly improve survival and regress established tumors in a mouse model of proneural GBM, a molecular subtype of GBM. Surprisingly, CSF-1R inhibition did not deplete tumor-associated macrophages (TAMs) but instead altered their polarization, reducing their tumor-promoting functions. Glioma cells secreted survival factors such as GM-CSF and IFN-γ, which protected TAMs from CSF-1R-induced apoptosis. The study also identified gene signatures associated with improved survival in proneural GBM patients, suggesting that CSF-1R inhibition may be a promising therapeutic strategy for this subtype of GBM.The study investigates the therapeutic potential of colony-stimulating factor-1 receptor (CSF-1R) inhibition in glioblastoma multiforme (GBM), a highly aggressive form of brain cancer. CSF-1R inhibition was found to significantly improve survival and regress established tumors in a mouse model of proneural GBM, a molecular subtype of GBM. Surprisingly, CSF-1R inhibition did not deplete tumor-associated macrophages (TAMs) but instead altered their polarization, reducing their tumor-promoting functions. Glioma cells secreted survival factors such as GM-CSF and IFN-γ, which protected TAMs from CSF-1R-induced apoptosis. The study also identified gene signatures associated with improved survival in proneural GBM patients, suggesting that CSF-1R inhibition may be a promising therapeutic strategy for this subtype of GBM.