PMID- 20089706 OWN - NLM STAT- MEDLINE DCOM- 20100326 LR - 20210103 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 184 IP - 4 DP - 2010 Feb 15 TI - Peroxynitrite-dependent killing of cancer cells and presentation of released tumor antigens by activated dendritic cells. PG - 1876-84 LID - 10.4049/jimmunol.0900831 [doi] AB - Dendritic cells (DCs), essential for the initiation and regulation of adaptive immune responses, have been used as anticancer vaccines. DCs may also directly trigger tumor cell death. In the current study, we have investigated the tumoricidal and immunostimulatory activities of mouse bone marrow-derived DCs. Our results indicate that these cells acquire killing capabilities toward tumor cells only when activated with LPS or Pam3Cys-SK4. Using different transgenic mouse models including inducible NO synthase or GP91 knockout mice, we have further established that LPS- or Pam3Cys-SK4-activated DC killing activity involves peroxynitrites. Importantly, after killing of cancer cells, DCs are capable of engulfing dead tumor cell fragments and of presenting tumor Ags to specific T lymphocytes. Thus, upon specific stimulation, mouse bone marrow-derived DCs can directly kill tumor cells through a novel peroxynitrite-dependent mechanism and participate at virtually all levels of antitumor immune responses, which reinforces their interest in immunotherapy. FAU - Fraszczak, Jennifer AU - Fraszczak J AD - Institut National de la Sante et de la Recherche Medicale Unite Mixte de Recherche 866, Institut de Recherche Federatif 100, Universite de Bourgogne, Dijon, France. FAU - Trad, Malika AU - Trad M FAU - Janikashvili, Nona AU - Janikashvili N FAU - Cathelin, Dominique AU - Cathelin D FAU - Lakomy, Daniela AU - Lakomy D FAU - Granci, Virginie AU - Granci V FAU - Morizot, Alexandre AU - Morizot A FAU - Audia, Sylvain AU - Audia S FAU - Micheau, Olivier AU - Micheau O FAU - Lagrost, Laurent AU - Lagrost L FAU - Katsanis, Emmanuel AU - Katsanis E FAU - Solary, Eric AU - Solary E FAU - Larmonier, Nicolas AU - Larmonier N FAU - Bonnotte, Bernard AU - Bonnotte B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100120 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, Neoplasm) RN - 14691-52-2 (Peroxynitrous Acid) SB - IM MH - Animals MH - Antigen Presentation/*immunology MH - Antigens, Neoplasm/*immunology/*metabolism MH - Cell Death/immunology MH - Cell Line, Tumor MH - Coculture Techniques MH - Dendritic Cells/*immunology/*metabolism MH - HeLa Cells MH - Humans MH - Melanoma, Experimental MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mice, Transgenic MH - Neoplasms, Experimental/*immunology/metabolism/*pathology MH - Peroxynitrous Acid/*toxicity EDAT- 2010/01/22 06:00 MHDA- 2010/03/27 06:00 CRDT- 2010/01/22 06:00 PHST- 2010/01/22 06:00 [entrez] PHST- 2010/01/22 06:00 [pubmed] PHST- 2010/03/27 06:00 [medline] AID - jimmunol.0900831 [pii] AID - 10.4049/jimmunol.0900831 [doi] PST - ppublish SO - J Immunol. 2010 Feb 15;184(4):1876-84. doi: 10.4049/jimmunol.0900831. Epub 2010 Jan 20.