Cytotoxic dendritic cells generated from cancer patients.

Daniela Lakomy (1) , Nona Janikashvili (2) , Jennifer Fraszczak (2) , Malika Trad (2) , Sylvain Audia (2, 3) , Maxime Samson (2, 3) , Marion Ciudad (2) , Julien Vinit (1) , Catherine Vergely (4) , Denis Caillot (1) , Pascal Foucher (5) , Laurent Lagrost (4) , Salem Chouaib (6) , Emmanuel Katsanis (7) , Nicolas Larmonier (7) , Bernard Bonnotte (2, 3)

1 CHU Dijon
2 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
3 Hôpital du Bocage
4 LNC - Lipides - Nutrition - Cancer (U866)
5 TRACES - Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés
6 U753 - Cytokines et Immunologie des Tumeurs Humaines
7 Steele Children's Research Center

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.

Domaines: Sciences du Vivant [q-bio]

Daniela Lakomy, Nona Janikashvili, Jennifer Fraszczak, Malika Trad, Sylvain Audia, et al.. Cytotoxic dendritic cells generated from cancer patients.. Journal of Immunology, 2011, 187 (5), pp.2775-82. ⟨10.4049/jimmunol.1004146⟩. ⟨hal-00828336⟩