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.
abstract: 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 IFNγ 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 IFNγ 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.
authors.affiliation: Department of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Romana
authors.initials: R
authors.lastname: Mikyšková
authors.affiliation: Department of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Štěpánek
authors.affiliation: Department of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Indrová
authors.affiliation: Department of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Bieblová
authors.affiliation: Department of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Šímová
authors.affiliation: SOTIO a.s., Prague, Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Truxová
authors.affiliation: SOTIO a.s., Prague, Czech Republic.
authors.forename: Irena
authors.initials: I
authors.lastname: Moserová
authors.affiliation: Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Fučíková
authors.affiliation: Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jiřina
authors.initials: J
authors.lastname: Bartůňková
authors.affiliation: Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Špíšek
authors.affiliation: Department of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Reiniš
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D019496:Cancer Vaccines / Q000737:chemistry; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology*; D000077143:Docetaxel; D006801:Humans; D006874:Hydrostatic Pressure; D007107:Immune System; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000628:therapy*; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000628:therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D013154:Spleen / Q000276:immunology; D043823:Taxoids / Q000008:administration & dosage*; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D043823:Taxoids; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D000077143:Docetaxel; D018664:Interleukin-12; D007371:Interferon-gamma