title: Cytotoxic dendritic cells generated from cancer patients.
abstract: Known for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies.
authors.affiliation: INSERM Unité Mixte de Recherche 866, Institut de Recherche Fédératif 100, Faculté de Médecine, 21079 Dijon, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lakomy
authors.forename: Nona
authors.initials: N
authors.lastname: Janikashvili
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fraszczak
authors.forename: Malika
authors.initials: M
authors.lastname: Trad
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.forename: Maxime
authors.initials: M
authors.lastname: Samson
authors.forename: Marion
authors.initials: M
authors.lastname: Ciudad
authors.forename: Julien
authors.initials: J
authors.lastname: Vinit
authors.forename: Catherine
authors.initials: C
authors.lastname: Vergely
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.forename: Pascal
authors.initials: P
authors.lastname: Foucher
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D030421:Peroxynitrous Acid / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D030421:Peroxynitrous Acid