Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure induce strong immune responses and display therapeutic effects both in murine TC-1 and TRAMP-C2 tumors when combined with docetaxel chemotherapy

0472944 - ÚMG 2017 RIV GR eng J - Článek v odborném periodiku
Mikyšková, Romana - Štěpánek, Ivan - Indrová, Marie - Bieblová, Jana - Šímová, Jana - Truxová, I. - Moserová, I. - Fučíková, J. - Bartunkova, J. - Špíšek, R. - Reiniš, Milan
Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure induce strong immune responses and display therapeutic effects both in murine TC-1 and TRAMP-C2 tumors when combined with docetaxel chemotherapy.
International Journal of Oncology. Roč. 48, č. 3 (2016), s. 953-964. ISSN 1019-6439. E-ISSN 1791-2423
Grant CEP: GA MŠMT(CZ) LM2011032; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:68378050
Klíčová slova: dendritic cells * docetaxel * high hydrostatic pressure * immunotherapy * cancer
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 3.079, rok: 2016

High hydrostatic pressure (HHP) has been shown to induce immunogenic cell death of cancer cells, facilitating their uptake by dendritic cells (DC) and subsequent presentation of tumor antigens. In the present study, we demonstrated immunogenicity of the HHP-treated tumor cells in mice. HHP was able to induce immunogenic cell death of both TC-1 and TRAMP-C2 tumor cells, representing murine models for human papilloma virus-associated tumors and prostate cancer, respectively. HHP-treated cells induced stronger immune responses in mice immunized with these tumor cells, documented by higher spleen cell cytotoxicity and increased IFN gamma production as compared to irradiated tumor cells, accompanied by suppression of tumor growth in vivo in the case of TC-1 tumors, but not TRAMP-C2 tumors. Furthermore, HHP-treated cells were used for DC-based vaccine antigen pulsing. DC co-cultured with HHP-treated tumor cells and matured by a TLR 9 agonist exhibited higher cell surface expression of maturation markers and production of IL-12 and other cytokines, as compared to the DC pulsed with irradiated tumor cells. Immunization with DC cell-based vaccines pulsed with HHP-treated tumor cells induced high immune responses, detected by increased spleen cell cytotoxicity and elevated IFN gamma production. The DC-based vaccine pulsed with HHP-treated tumor cells combined with docetaxel chemotherapy significantly inhibited growth of both TC-1 and TRAMP-C2 tumors. Our results indicate that DC-based vaccines pulsed with HHP-inactivated tumor cells can be a suitable tool for chemoimmunotherapy, particularly with regard to the findings that poorly immunogenic TRAMP-C2 tumors were susceptible to this treatment modality.
Trvalý link: http://hdl.handle.net/11104/0270136