Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism
Fiche publication
Date publication
juillet 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BONNOTTE Bernard
Tous les auteurs :
Nicolas A, Cathelin D, Larmonier N, Fraszczak J, Puig PE, Bouchot A, Bateman A, Solary E, Bonnotte B
Lien Pubmed
Résumé
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 (BNMCs) 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 LIPS 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 BNMCs represent powerful tumoricidal cells which enforce their potential as anticancer cellular vaccines.
Référence
J Immunol. 2007 Jul 15;179(2):812-8.