Cytotoxic dendritic cells generated from cancer patients

Daniela Lakomy, Nona Janikashvili, Jennifer Fraszczak, Malika Trad, Sylvain Audia, Maxime Samson, Marion Ciudad, Julien Vinit, Catherine Vergely, Denis Caillot, Pascal Foucher, Laurent Lagrost, Salem Chouaib, Emmanuel Katsanis, Nicolas Larmonier, Bernard Bonnotte

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Known for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies.

Original languageEnglish (US)
Pages (from-to)2775-2782
Number of pages8
JournalJournal of Immunology
Volume187
Issue number5
DOIs
StatePublished - Sep 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lakomy, D., Janikashvili, N., Fraszczak, J., Trad, M., Audia, S., Samson, M., Ciudad, M., Vinit, J., Vergely, C., Caillot, D., Foucher, P., Lagrost, L., Chouaib, S., Katsanis, E., Larmonier, N., & Bonnotte, B. (2011). Cytotoxic dendritic cells generated from cancer patients. Journal of Immunology, 187(5), 2775-2782. https://doi.org/10.4049/jimmunol.1004146