Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism

Alexandra Nicolas, Dominique Cathelin, Nicolas Larmonier, Jennifer Fraszczak, Pierre Emmanuel Puig, André Bouchot, Andrew Bateman, Eric Solary, Bernard Bonnotte

Research output: Contribution to journalArticle

30 Scopus citations

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-γ-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-α, 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.

Original languageEnglish (US)
Pages (from-to)812-818
Number of pages7
JournalJournal of Immunology
Volume179
Issue number2
DOIs
StatePublished - Jul 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nicolas, A., Cathelin, D., Larmonier, N., Fraszczak, J., Puig, P. E., Bouchot, A., Bateman, A., Solary, E., & Bonnotte, B. (2007). Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism. Journal of Immunology, 179(2), 812-818. https://doi.org/10.4049/jimmunol.179.2.812