Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism |
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Authors: | Nicolas Alexandra Cathelin Dominique Larmonier Nicolas Fraszczak Jennifer Puig Pierre-Emmanuel Bouchot André Bateman Andrew Solary Eric Bonnotte Bernard |
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Institution: | 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. |
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Abstract: | 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. |
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