Tumor associated macrophages (TAM) can promote angiogenesis, invasiveness and 
immunosuppression. The cytokine CSF-1 (or M-CSF) is an important factor of TAM 
recruitment and differentiation and several pharmacological agents targeting the 
CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We 
show that the kinase inhibitor PLX3397 strongly dampened the systemic and local 
accumulation of macrophages driven by B16F10 melanomas, without affecting 
Gr-1(+) myeloid derived suppressor cells. Removal of intratumoral macrophages 
was remarkably efficient and a modest, but statistically significant, delay in 
melanoma outgrowth was observed. Importantly, CSF-1R inhibition strongly 
enhanced tumor control by immunotherapy using tumor-specific CD8 T cells. 
Elevated IFNγ production by T cells was observed in mice treated with the 
combination of PLX3397 and immunotherapy. These results support the combined use 
of CSF-1R inhibition with CD8 T cell immunotherapy, especially for 
macrophage-stimulating tumors.