Metronomic paclitaxel improves the efficacy of PD-1 monoclonal antibodies in breast cancer by transforming the tumor immune microenvironment

Abstract

The clinical efficacy of PD-1/PD-L1 monoclonal antibodies (mAbs) in triple-negative breast cancer (TNBC) is unsatisfactory. Immunotherapy combined with chemotherapy shows good therapeutic potential. Preclinical and clinical studies have shown that metronomic chemotherapy may stimulate anticancer immune responses. We aimed to verify whether metronomic paclitaxel (PTX, TAX) treatment can improve the efficacy of a PD-1 mAb in a TNBC mouse model and to explore the potential mechanism. After constructing the TNBC mouse model and treating with PD-1 mAb, metronomic PTX chemotherapy or combined therapy, the differences in the efficacy of each treatment group were compared and analyzed. Our findings suggested that the combination of metronomic PTX chemotherapy and PD-1 mAb produces a potent antitumor effect. Further experiments demonstrated that metronomic PTX chemotherapy changed the immune cell population in tumor tissues. These data suggest that metronomic PTX improves the efficacy of the PD-1 mAb in TNBC by transforming the tumor immune microenvironment, and these results provide strong evidence for the use of this treatment in TNBC patients in the future.

Keywords: Metronomic chemotherapy; PD-1; breast cancer; immunotherapy; paclitaxel.