Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism.
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.
Nicolas
Alexandra
A
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.
Cathelin
Dominique
D
Larmonier
Nicolas
N
Fraszczak
Jennifer
J
Puig
Pierre-Emmanuel
PE
Bouchot
André
A
Bateman
Andrew
A
Solary
Eric
E
Bonnotte
Bernard
B
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
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D009569:Nitric Oxide