PMID- 11823515 OWN - NLM STAT- MEDLINE DCOM- 20020304 LR - 20201212 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 168 IP - 4 DP - 2002 Feb 15 TI - Innate direct anticancer effector function of human immature dendritic cells. I. Involvement of an apoptosis-inducing pathway. PG - 1823-30 AB - Dendritic cells (DCs) mediate cross-priming of tumor-specific T cells by acquiring tumor Ags from dead cancer cells. The process of cross-priming would be most economical and efficient if DCs also induce death of cancer cells. In this study, we demonstrate that normal human in vitro generated immature DCs consistently and efficiently induce apoptosis in cancer cell lines, freshly isolated noncultured cancer cells, and normal proliferating endothelial cells, but not in most normal cells. In addition, in vivo generated noncultured peripheral blood immature DCs mediate similar tumoricidal activity as their in vitro counterpart, indicating that this DC activity might be biologically relevant. In contrast to immature DCs, freshly isolated monocytes (myeloid DC precursors) and in vitro generated mature DCs are not cytotoxic or are less cytotoxic, respectively, suggesting that DC-mediated killing of cancer cells is developmentally regulated. Comparable cytotoxic activity is mediated by untreated DCs, paraformaldehyde-fixed DCs, and soluble products of DCs, and is destructible by proteases, indicating that both cell membrane-bound and secreted proteins mediate this DC function. Overall, our data demonstrate that human immature DCs are capable of inducing apoptosis in cancer cells and thus to both directly mediate anticancer activity and initiate processing of cellular tumor Ags. FAU - Janjic, Bratislav M AU - Janjic BM AD - University of Pittsburgh Cancer Institute, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15231, USA. FAU - Lu, Ganwei AU - Lu G FAU - Pimenov, Alexei AU - Pimenov A FAU - Whiteside, Theresa L AU - Whiteside TL FAU - Storkus, Walter J AU - Storkus WJ FAU - Vujanovic, Nikola L AU - Vujanovic NL LA - eng GR - 1-PO DE13059-01/DE/NIDCR NIH HHS/United States GR - R01 CA 82016/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Culture Media, Conditioned) RN - 0 (Membrane Proteins) RN - EC 3.4.22.- (Caspases) SB - IM MH - *Apoptosis MH - Caspases/physiology MH - Cell Line MH - Cells, Cultured MH - Culture Media, Conditioned/pharmacology MH - Cytotoxicity Tests, Immunologic MH - Dendritic Cells/classification/*immunology MH - Humans MH - Immunophenotyping MH - Kinetics MH - Membrane Proteins/physiology MH - Monocytes/immunology MH - Neoplasms/*immunology/pathology MH - Signal Transduction MH - Stem Cells/immunology MH - Tumor Cells, Cultured EDAT- 2002/02/02 10:00 MHDA- 2002/03/05 10:01 CRDT- 2002/02/02 10:00 PHST- 2002/02/02 10:00 [pubmed] PHST- 2002/03/05 10:01 [medline] PHST- 2002/02/02 10:00 [entrez] AID - 10.4049/jimmunol.168.4.1823 [doi] PST - ppublish SO - J Immunol. 2002 Feb 15;168(4):1823-30. doi: 10.4049/jimmunol.168.4.1823.