Immature dendritic cells kill ovarian carcinoma cells by a Fas/FasL pathway, enabling them to sensitize tumor-specific CTLs

Dendritic cells (DCs) can acquire antigen(s) from apoptotic tumor cells, re sulting in an immunogen that can induce class I-restricted cytotoxic T lymp hocytes (CTLs) and protective tumor rejection. Here, we investigated whethe r DCs derived from ascitic monocytes of patients with ovarian carcinoma cou ld kill autologous ovarian tumor cells and if as a result they would acquir e antigen(s) enabling them to induce a tumor-specific immunity. We found th at the immature DCs could exert a significant cytotoxicity towards autologo us and allogeneic ovarian tumor cells. This cytotoxicity was independent of Ca2+ and could be inhibited by anti-Fas IgG I monoclonal antibody, indicat ing the involvement of the Fas/Fas ligand (FasL) pathway in the cytotoxic m echanism. Further supporting this conclusion, the ascitic monocyte-derived DCs expressed high levels of FasL mRNA and intracellular FasL and significa nt levels of Fas were also revealed on the surface of ovarian tumor cells. Coculture of DCs induced apoptosis in ovarian carcinoma cells, as well as u ptake of apoptotic tumor cells into the cytoplasma of the DCs, as visualize d by immunofluoresence. Autologous DCs cocultured with apoptotic ovarian tu mor cells were able to specifically stimulate tumor-specific CTLs, whereas DCs cocultured with necrotic ovarian cells were unable to do so. Collective ly, these results demonstrate that immature DCs can kill autologous ovarian carcinoma cells via the Ca2+-independent Fas/FasL pathway and that this ma y have important consequences for their ability to stimulate tumor-specific CTLs. (C) 2001 Wiley-Liss, Inc.