Introduction We evaluated the effect of decitabine on T-cell mediated immunity in ovarian cancer cell lines when combined with topoisomerase I inhibitors

Methods We selected five human (ES2, OV90, SKOV3, TOV21G, TOV112D) and one mouse ovarian cancer lines (ID8). After we selected belotecan after comparison of the cytotoxic effect with topotecan, we determined the concentration of decitabine not showing the additive cytotoxic effect when combined with belotecan. We administered decitabine of 0.25 mg/kg six times every two days, followed by belotecan of 0.17 mg/kg five times daily eight weeks after we inoculated ID8 cells in the subcutaneous layer of C57BL/6, and then evaluated T-cell immunity in the spleen and tumor cells with expressions of PD-1 and CTLA4.

Results The cytotoxic effect of belotecan was superior to that of topotecan in the six cell lines, and mRNA expressions of PD-L1, TNF, IL6 and TFGβ were increased in ES2, SKOV3, TOV21G and TOV112D cell lines. Moreover, the low concentration of decitabine did not show the additive cytotoxic effect when combined with belotecan, whereas decitabine increased apoptosis by belotecan synergically in the five human ovarian cancer cell lines. Even though PD-1 and CTLA4 were not increased in the allograft C57BL/6 mouse by ID8, CD3+CD8+T cells were increased after administration of belotecan and decitabine in the spleen and tumor cells.

Conclusion/Implications Even though decitabine dose not increase expressions of PD-1 and CTLA4 as targets of immune checkpoint inhibitors, it may increase CD3+CD8+T cells in the spleen and ovarian cancer cells when combined with belotecan.