CIS-platin increases immune activity of monocytes and cytotoxic T-cells in a murine model of epithelial ovarian cancer

Highlights

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  CIS-platin chemotherapy leads to an increase in the percentage of monocytes within the ascites in a murine model of epithelial ovarian cancer.

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  Ascites derived CD11b ⁺ cells elicit an increased response from T-cells after treatment with CIS-platin.

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  CIS-platin chemotherapy increases tumor-antigen -specific IFN-ɣ responses from T-cells.

Abstract

Epithelial ovarian cancer (EOC) is an immunologically active malignancy, but thus far immune therapy has had limited success in clinical trials. One barrier to implementation of efficacious immune therapies is a lack of knowledge of the effect of chemotherapy on the monocyte-derived component of the immune infiltrate within the tumor. We utilized the ID8 murine EOC model to investigate alterations within tumor ascites that occur following administration of platinum chemotherapy. Cisplatin treatment resulted in a significant increase in monocytes within the ascites of tumor bearing mice. We identified that CD11b ⁺ cells from the ascites of mice that have been treated with cisplatin elicits an increase in IFN-ɣ expression from CD8 ⁺ T-cells compared to CD11b ⁺ cells from a mouse treated with vehicle control (604.0 pg/mL v. 4328.0 pg/mL; p < .0001). Splenocytes derived from tumor bearing mice released increase levels of IFN-ɣ after treatment with cisplatin when incubated with dendritic cells (DCs) and tumor antigen (62.0 v. 92.1 pg/mL; p = .03). CIS-platin induced an increase in T-cell and monocyte/macrophage activation markers (CD62L and CD301). Levels of IL-10, IL-6, and VEGF in the cell free ascites of mice treated with CIS-platin decreased ( p > .05). These results indicate that treatment with cisplatin leads to an increase of anti-tumor activity within the ascites related to alterations in the ascites monocytes. Further investigation of these findings in humans is necessary to identify how these cells behave in different patient subgroups and if there is a role for monocyte directed therapy in conjunction with T-cell directed therapy and/or chemotherapy.