Abstract

BACKGROUND: The main purpose of this study was to explore the antitumor effect and mechanisms of ACAT1 inhibitor combined with CSCs-DC vaccine.

MATERIAL AND METHODS: We isolated HNSCC CSCs and gained CSCs antigens, then used CSCs antigens to load dendritic cells (DC) and generated a CSCs-DC vaccine. We treated mice after surgical excision of established SCC7 tumors with CSCs-DC vaccine and/or ACAT1 inhibitor, and recorded local tumor relapse and host survival. T cells and B cells were harvested from mice treated with CSCs-DC vaccine and/or ACAT1 inhibitor. We tested antibody production and the death rate of CSCs killed by T cells.

RESULTS: The tumors in the combined treatment group were smaller than in all other groups (P<0.01). The average survival time of the combined treatment group was 82 days and was the longest of all groups. Analysis of IgG levels secreted by B cell and CTL activity in spleens of mice found that results of the combined treatment group were the highest, and the results of the CSCs-DC group were lower than in the combined treatment group. The ACAT1 inhibitor group results were lower than in the CSCs-DC group and the combined treatment group results, but higher than in the PBS group, and the difference was statistically significant.

CONCLUSIONS: ACAT1 inhibitor enhanced the therapeutic effect of CSCs-DC vaccine in the treatment of the mouse HNSCC postoperative recurrence model. ACAT1 may play an important role in cancer immunotherapy.

Keywords: Head and Neck Neoplasms, Neoplastic Stem Cells, Sterol O-Acyltransferase