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.
↵2 N.L. and B.B. share senior authorship.
This work was supported by grants from La Ligue contre le Cancer (to B.B.), the Conseil Régional de Bourgogne (to B.B.), and the University Hospital of Dijon (to B.B.), as well as National Institutes of Health Grant R01 CA104926 (to E.K. and N.L.), Arizona Cancer Center Support Grant CA023074 (to E.K. and N.L.), and funds from Tee Up for Tots and People Acting Now Discover Answers (to E.K. and N.L.).
The online version of this article contains supplemental material.
- Received December 22, 2010.
- Accepted June 26, 2011.
- Copyright © 2011 by The American Association of Immunologists, Inc.