Cytotoxic Dendritic Cells Generated from Cancer Patients

International audienceKnown for years as professional antigen presenting cells (APC), dendritic cells (DC) 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 DC has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms including the induction of immunosuppressive/tolerogenic DC which have lost their ability to present antigens in an immunogenic manner. We herein evaluate the possibility of generating tumor killer DC from patients with advanced stage cancers. We demonstrate that human monocyte-derived DC 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 DC. Additionally, after killing, these cytotoxic DC are able to activate tumor Ag specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DC in cancer immunotherapy strategies