PMID- 17617571 OWN - NLM STAT- MEDLINE DCOM- 20070919 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 179 IP - 2 DP - 2007 Jul 15 TI - Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism. PG - 812-8 AB - 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. FAU - Nicolas, Alexandra AU - Nicolas A AD - Institut National de la Sante et de la Recherche Medicale Unit Mixte de Recherche 866, Institut Federatif de Recherche 100, Universite de Bourgogne, Dijon, France. FAU - Cathelin, Dominique AU - Cathelin D FAU - Larmonier, Nicolas AU - Larmonier N FAU - Fraszczak, Jennifer AU - Fraszczak J FAU - Puig, Pierre-Emmanuel AU - Puig PE FAU - Bouchot, Andre AU - Bouchot A FAU - Bateman, Andrew AU - Bateman A FAU - Solary, Eric AU - Solary E FAU - Bonnotte, Bernard AU - Bonnotte B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Adjuvants, Immunologic) RN - 0 (Lipopolysaccharides) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Adjuvants, Immunologic/pharmacology MH - Animals MH - Blotting, Western MH - Bone Marrow Cells/immunology MH - Cell Death/*physiology MH - Cell Line, Tumor MH - *Cytotoxicity, Immunologic MH - Dendritic Cells/drug effects/*metabolism MH - Flow Cytometry MH - Humans MH - Lipopolysaccharides/pharmacology MH - Neoplasms/*immunology MH - Nitric Oxide/*metabolism MH - Rats EDAT- 2007/07/10 09:00 MHDA- 2007/09/20 09:00 CRDT- 2007/07/10 09:00 PHST- 2007/07/10 09:00 [pubmed] PHST- 2007/09/20 09:00 [medline] PHST- 2007/07/10 09:00 [entrez] AID - 179/2/812 [pii] AID - 10.4049/jimmunol.179.2.812 [doi] PST - ppublish SO - J Immunol. 2007 Jul 15;179(2):812-8. doi: 10.4049/jimmunol.179.2.812.