Peroxynitrite-dependent killing of cancer cells and presentation of released tumor antigens by activated dendritic cells

Jennifer Fraszczak, Malika Trad, Nona Janikashvili, Dominique Cathelin, Daniela Lakomy, Virginie Granci, Alexandre Morizot, Sylvain Audia, Olivier Micheau, Laurent Lagrost, Emmanuel Katsanis, Eric Solary, Nicolas Larmonier, Bernard Bonnotte

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Dendritic cells (DCs), essential for the initiation and regulation of adaptive immune responses, have been used as anticancer vaccines. DCs may also directly trigger tumor cell death. In the current study, we have investigated the tumoricidal and immunostimulatory activities of mouse bone marrow-derived DCs. Our results indicate that these cells acquire killing capabilities toward tumor cells only when activated with LPS or Pam3Cys-SK4. Using different transgenic mouse models including inducible NO synthase or GP91 knockout mice, we have further established that LPS- or Pam3Cys-SK4-activated DC killing activity involves peroxynitrites. Importantly, after killing of cancer cells, DCs are capable of engulfing dead tumor cell fragments and of presenting tumor Ags to specific T lymphocytes. Thus, upon specific stimulation, mouse bone marrow-derived DCs can directly kill tumor cells through a novel peroxynitrite-dependent mechanism and participate at virtually all levels of antitumor immune responses, which reinforces their interest in immunotherapy.

Original languageEnglish (US)
Pages (from-to)1876-1884
Number of pages9
JournalJournal of Immunology
Volume184
Issue number4
DOIs
StatePublished - Feb 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Fraszczak, J., Trad, M., Janikashvili, N., Cathelin, D., Lakomy, D., Granci, V., Morizot, A., Audia, S., Micheau, O., Lagrost, L., Katsanis, E., Solary, E., Larmonier, N., & Bonnotte, B. (2010). Peroxynitrite-dependent killing of cancer cells and presentation of released tumor antigens by activated dendritic cells. Journal of Immunology, 184(4), 1876-1884. https://doi.org/10.4049/jimmunol.0900831