Colony-stimulating factor 1 receptor: a novel target for cancer immunotherapy

Abstract

The Colony-Stimulating Factor 1 (CSF-1) and its receptor (CSF1R) constitute an important axis that regulates the phenotype of most tissue-resident macrophages. Endogenous cytokine ligation and oncogenic mutations of CSF1R trigger the activation of several downstream pro-survival kinase cascades, thereby enhancing tumor cell proliferation and disease progression. Tumor-associate macrophages (TAMs) harboring activated CSF1R release tumorigenic cytokines, thus further deconditioning tumor immune microenvironment to a pro-tumoral phenotype. With the recent success of pexidartinib for the treatment of tenosynovial giant cell tumor, CSF1R pathway blockage has emerged as a promising TAM-targeting approach in certain types of cancers. More interventions to CSF1R, including monotherapy and combinatorial therapy, have advanced to clinical trials for a broader spectrum of cancers, highlighting such strategy to benefit cancer immunotherapy.