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* 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;
Department of Pediatrics, Steele Children’s Research Center, University of Arizona, Tucson, AZ 85724;
Plateau Technique d’Imagerie Cellulaire, Institut Fédératif de Recherche 100, Université de Bourgogne, Dijon, France; and
Somers Cancer Research Building, Southampton General Hospital, Southampton, United Kingdom
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-
-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-
, 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Burgundy Committee of the French National League against Cancer and the Tee Up for Tots and Raise a Racquet Funds (to N.L.). D.C. received financial support from the Saône-et-Loire Committee of the French National League Against Cancer.
2 A.N. and D.C. contributed equally to this work.
3 Address correspondence and reprint requests to Prof. Bernard Bonnotte, Institut National de la Santé et de la Recherche Médicale Unit Mixte de Recherche 866, Institut Fédératif de Recherche 100, Université de Bourgogne, 7 Bd Jeanne d’Arc, Dijon, France. E-mail address: bernard.bonnotte{at}u-bourgogne.fr
4 Abbreviations used in this paper: DC, dendritic cell; NKR-P1, NK cell receptor protein 1; BMDC, bone marrow-derived cytotoxic DC; FasL, Fas ligand; NMMA, NG-methyl-L-arginine; CM, complete medium; iNOS, inducible NO synthase.
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