Tumoricidal potential of native blood dendritic cells: direct tumor cell killing and activation of NK cell-mediated cytotoxicity.
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.
Schmitz
Marc
M
Institute of Immunology, Medical Faculty, Technical University of Dresden, Dresden, Germany. mschmitz@rcs.urz.tu-dresden.de <mschmitz@rcs.urz.tu-dresden.de>
Zhao
Senming
S
Deuse
Yvonne
Y
Schäkel
Knut
K
Wehner
Rebekka
R
Wöhner
Hanka
H
Hölig
Kristina
K
Wienforth
Florian
F
Kiessling
Andrea
A
Bornhäuser
Martin
M
Temme
Achim
A
Rieger
Michael A
MA
Weigle
Bernd
B
Bachmann
Michael
M
Rieber
E Peter
EP
D001773:Blood Cells; D016827:CD8 Antigens; D002450:Cell Communication; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology
D016827:CD8 Antigens; D014409:Tumor Necrosis Factor-alpha