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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
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SYSNO ASEP 0472944 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title 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 Author(s) Mikyšková, Romana (UMG-J) RID
Štěpánek, Ivan (UMG-J) RID
Indrová, Marie (UMG-J) RID
Bieblová, Jana (UMG-J)
Šímová, Jana (UMG-J) RID
Truxová, I. (CZ)
Moserová, I. (CZ)
Fučíková, J. (CZ)
Bartunkova, J. (CZ)
Špíšek, R. (CZ)
Reiniš, Milan (UMG-J) RIDNumber of authors 11 Source Title International Journal of Oncology. - : Spandidos Publications - ISSN 1019-6439
Roč. 48, č. 3 (2016), s. 953-964Number of pages 12 s. Language eng - English Country GR - Greece Keywords dendritic cells ; docetaxel ; high hydrostatic pressure ; immunotherapy ; cancer Subject RIV EB - Genetics ; Molecular Biology R&D Projects LM2011032 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMG-J - RVO:68378050 UT WOS 000369185000011 DOI 10.3892/ijo.2015.3314 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2017
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