PMID- 15778372 OWN - NLM STAT- MEDLINE DCOM- 20050607 LR - 20201226 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 174 IP - 7 DP - 2005 Apr 1 TI - Tumoricidal potential of native blood dendritic cells: direct tumor cell killing and activation of NK cell-mediated cytotoxicity. PG - 4127-34 AB - Dendritic cells (DCs) are characterized by their unique capacity for primary T cell activation, providing the opportunity for DC-based cancer vaccination protocols. Novel findings reveal that besides their role as potent inducers of tumor-specific T cells, human DCs display additional antitumor effects. Most of these data were obtained with monocyte-derived DCs, whereas studies investigating native blood DCs are limited. In the present study, we analyze the tumoricidal capacity of M-DC8(+) DCs, which represent a major subpopulation of human blood DCs. We demonstrate that IFN-gamma-stimulated M-DC8(+) DCs lyse different tumor cell lines but not normal cells. In addition, we show that tumor cells markedly enhance the production of TNF-alpha by M-DC8(+) DCs via cell-to-cell contact and that this molecule essentially contributes to the killing activity of M-DC8(+) DCs. Furthermore, we illustrate the ability of M-DC8(+) DCs to promote proliferation, IFN-gamma production, and tumor-directed cytotoxicity of NK cells. The M-DC8(+) DC-mediated enhancement of the tumoricidal potential of NK cells is mainly dependent on cell-to-cell contact. These results reveal that, in addition to their crucial role in activating tumor-specific T cells, blood DCs exhibit direct tumor cell killing and enhance the tumoricidal activity of NK cells. These findings point to the pivotal role of DCs in triggering innate and adaptive immune responses against tumors. FAU - Schmitz, Marc AU - Schmitz M AD - Institute of Immunology, Medical Faculty, Technical University of Dresden, Dresden, Germany. mschmitz@rcs.urz.tu-dresden.de FAU - Zhao, Senming AU - Zhao S FAU - Deuse, Yvonne AU - Deuse Y FAU - Schakel, Knut AU - Schakel K FAU - Wehner, Rebekka AU - Wehner R FAU - Wohner, Hanka AU - Wohner H FAU - Holig, Kristina AU - Holig K FAU - Wienforth, Florian AU - Wienforth F FAU - Kiessling, Andrea AU - Kiessling A FAU - Bornhauser, Martin AU - Bornhauser M FAU - Temme, Achim AU - Temme A FAU - Rieger, Michael A AU - Rieger MA FAU - Weigle, Bernd AU - Weigle B FAU - Bachmann, Michael AU - Bachmann M FAU - Rieber, E Peter AU - Rieber EP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (CD8 Antigens) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Blood Cells MH - CD8 Antigens MH - Cell Communication MH - Cell Line, Tumor MH - *Cytotoxicity, Immunologic MH - Dendritic Cells/cytology/*immunology MH - Humans MH - Immunity MH - Killer Cells, Natural/*immunology MH - Lymphocyte Activation/immunology MH - Neoplasms/immunology/*pathology MH - Tumor Necrosis Factor-alpha/biosynthesis/physiology EDAT- 2005/03/22 09:00 MHDA- 2005/06/09 09:00 CRDT- 2005/03/22 09:00 PHST- 2005/03/22 09:00 [pubmed] PHST- 2005/06/09 09:00 [medline] PHST- 2005/03/22 09:00 [entrez] AID - 174/7/4127 [pii] AID - 10.4049/jimmunol.174.7.4127 [doi] PST - ppublish SO - J Immunol. 2005 Apr 1;174(7):4127-34. doi: 10.4049/jimmunol.174.7.4127.