title: Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism.
abstract: Dendritic cells (DCs) are well known for their capacity to induce adaptive antitumor immune response through Ag presentation and tumor-specific T cell activation. Recent findings reveal that besides this role, DCs may display additional antitumor effects. In this study, we provide evidence that LPS- or IFN-gamma-activated rat bone marrow-derived dendritic cells (BMDCs) display killing properties against tumor cells. These cytotoxic BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, and TNF-alpha, and retain their phagocytic properties. BMDC-mediated tumor cell killing requires cell-cell contact and depends on NO production, but not on perforin/granzyme or on death receptors. Furthermore, dead tumor cells do not exhibit characteristics of apoptosis. Thus, intratumoral LPS injections induce an increase of inducible NO synthase expression in tumor-infiltrating DCs associated with a significant arrest of tumor growth. Altogether, these results suggest that LPS-activated BMDCs represent powerful tumoricidal cells which enforce their potential as anticancer cellular vaccines.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unit Mixte de Recherche 866, Institut Fédératif de Recherche 100, Université de Bourgogne, Dijon, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nicolas
authors.forename: Dominique
authors.initials: D
authors.lastname: Cathelin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fraszczak
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Puig
authors.forename: André
authors.initials: A
authors.lastname: Bouchot
authors.forename: Andrew
authors.initials: A
authors.lastname: Bateman
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009369:Neoplasms / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats
chemical_list: D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D009569:Nitric Oxide