title: Peroxynitrite-dependent killing of cancer cells and presentation of released tumor antigens by activated dendritic cells.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 866, Institut de Recherche Fédératif 100, Université de Bourgogne, Dijon, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fraszczak
authors.forename: Malika
authors.initials: M
authors.lastname: Trad
authors.forename: Nona
authors.initials: N
authors.lastname: Janikashvili
authors.forename: Dominique
authors.initials: D
authors.lastname: Cathelin
authors.forename: Daniela
authors.initials: D
authors.lastname: Lakomy
authors.forename: Virginie
authors.initials: V
authors.lastname: Granci
authors.forename: Alexandre
authors.initials: A
authors.lastname: Morizot
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.forename: Olivier
authors.initials: O
authors.lastname: Micheau
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism*; D016923:Cell Death / Q000276:immunology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008546:Melanoma, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D030421:Peroxynitrous Acid / Q000633:toxicity*
chemical_list: D000951:Antigens, Neoplasm; D030421:Peroxynitrous Acid