Synergistic anti-tumor effects of dasatinib and dendritic cell vaccine on metastatic breast cancer in a mouse model.

Abstract

Immunotherapy is currently considered as one of the major anti-tumor modalities, but its efficacy is limited. Dasatinib could improve the expansion and recruitment of cluster of differentiation (CD) 8+T cells and natural killer (NK) cells to the tumor microenvironment. The present study aimed to evaluate the synergistic anti-tumor effects of dasatinib with dendritic cell (DC) vaccine in metastatic breast cancer. Dasatinib with DC vaccine was administered to mice inoculated with 4T1 breast cancer cells. Thereafter, tumor volume was measured every other day. On day 34, lung metastasis was assessed with a stereomicroscope. Tumor proliferation and angiogenesis were determined by immunohistochemistry. Apoptosis in tumor tissues was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling. The results showed that although there were no significant differences in tumor volumes between the untreated control, DC vaccine and dasatinib groups, the tumor volume was significantly decreased in the combined treatment group compared to the other three groups. Mice in the combined treatment group showed the longest survival time, while mice treated with either single treatment had a slightly increased survival time compared to the untreated control mice. Additionally, the number of metastatic lung nodules was significantly decreased in combined treatment group compared with the dasatinib alone, DC vaccine alone and untreated control groups. Furthermore, the combined treatment group showed significantly reduced intratumoral microvessel density compared to the other three groups. In addition, the ratios of CD8+ T and NK cells were significantly increased in the combined treatment group compared with the other three groups. These results suggest that dasatinib combined with the DC vaccine is a possible modality for the treatment of metastatic breast cancer.