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 Citations (Scopus)

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
StatePublished - Jul 15 2007

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Dendritic Cells
Nitric Oxide
Cell Death
Neoplasms
Bone Marrow
Granzymes
Perforin
Death Domain Receptors
Adaptive Immunity
Interleukin-12
Nitric Oxide Synthase
Interleukin-6
Vaccines
Apoptosis
T-Lymphocytes
Phenotype
Injections
Growth

ASJC Scopus subject areas

  • Immunology

Cite this

Nicolas, A., Cathelin, D., Larmonier, N., Fraszczak, J., Puig, P. E., Bouchot, A., ... Bonnotte, B. (2007). Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism. Journal of Immunology, 179(2), 812-818.

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

In: Journal of Immunology, Vol. 179, No. 2, 15.07.2007, p. 812-818.

Research output: Contribution to journalArticle

Nicolas, A, Cathelin, D, Larmonier, N, Fraszczak, J, Puig, PE, Bouchot, A, Bateman, A, Solary, E & Bonnotte, B 2007, 'Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism', Journal of Immunology, vol. 179, no. 2, pp. 812-818.
Nicolas A, Cathelin D, Larmonier N, Fraszczak J, Puig PE, Bouchot A et al. Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism. Journal of Immunology. 2007 Jul 15;179(2):812-818.
Nicolas, Alexandra ; Cathelin, Dominique ; Larmonier, Nicolas ; Fraszczak, Jennifer ; Puig, Pierre Emmanuel ; Bouchot, André ; Bateman, Andrew ; Solary, Eric ; Bonnotte, Bernard. / Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism. In: Journal of Immunology. 2007 ; Vol. 179, No. 2. pp. 812-818.
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