Immunogenicities of apoptotic ovarian cancer cells induced by paclitaxel combined with cisplatin
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Abstract:
Objective: To explore whether apoptotic ovarian cancer cells induced by chemotherapy drugs paclitaxel and cisplatin can be crosspresented by dendritic cells (DCs) and enhance immune responses. Methods: DCs were induced from peripheral blood monocytes cells by GMCSF/IL4 for 6 d, then they were stimulated with either apoptotic ovarian cancer HO8910 cells, frozenthawed HO8910 cells or control cells for 4 h. Their surface markers and phagocytotic ability were detected by flow cytometry and confocal microscopic scanning assay, respectively. DCs of different groups were cultured with CD8+ T cells isolated by magnetic cell sorting, and the ability of DCs to activate CD8+ T cells was evaluated by 3HTdR, the activity of CTL to kill tumor cells was evaluated by LDH. Production of IFNγ by CD8+ T cells was measured by ELISPOT. Results: Apoptotic ovarian cancer cells induced by chemotherapy drugs paclitaxel and cisplatin could be phagocytized by DCs, which subsequently promoted the maturation and antigen presenting ability of DCs. Apoptotic ovarian cancer cells implused DCs significantly promoted proliferation of CD8+ T cells compared with that of control cells (P<0.05); they also significantly increased the cytotocity of CTL to kill tumor cells compared with that of frozenthawed HO8910 cells and control cells as detected by LDH and ELISPOT(all P<0.01). Conclusion: Apoptotic ovarian cancer cells induced by paclitaxel and cisplatin exhibit strong immunogenicity and enhanced ability to promote DCs maturation and antigen presentation, subsequently enhance CD8+ T cell proliferation and promote their ability to secrete IFNγ and kill tumor cells.
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Supported by the Education Commission Research Project of Shanghai(No.061012)