Depletion of tumor-associated macrophages enhances the anti-tumor effect of docetaxel in a murine epithelial ovarian cancer

Abstract

Docetaxel (DTXL), a new member of the taxoid family, has been used for cancer treatment. However, increasing cases of DTXL resistance have been reported. Tumor-associated macrophages (TAMs) have been implicated in tumor invasion and chemo-resistance. Eliminating TAMs by inhibiting colony stimulating factor-1 receptor (CSF-1R) has emerged as a promising strategy for cancer treatment. BLZ945 is a CSF-1R inhibitor and has anti-tumor function. In present study, anti-tumor effects of combination treatment of BLZ945 and DTXL were investigated. We established a mouse ovarian cancer model and investigated the effect of BLZ945, DTXL single treatment or combination treatment on TAMs infiltration, tumor growth, CD8⁺ T cell infiltration and cancer metastasis. DTXL treatment increased the infiltration while BLZ945 induced cell apoptosis in macrophages. DTXL/BLZ945 combination treatment significantly inhibited tumor growth, reduced the abundance of TAMs, increased CD8⁺ T cell infiltration and prevented lung metastasis. Depletion of Tumor-Associated Macrophages (TAMs) by BLZ945 enhanced the anti-tumor effect of DTXL in a murine epithelial ovarian cancer.

Keywords: BLZ945; Depletion; Docetaxel; Ovarian cancer; Tumor-associated macrophages.