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 effe...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2005-04, Vol.174 (7), p.4127-4134
Main Authors: Schmitz, Marc, Zhao, Senming, Deuse, Yvonne, Schakel, Knut, Wehner, Rebekka, Wohner, Hanka, Holig, Kristina, Wienforth, Florian, Kiessling, Andrea, Bornhauser, Martin, Temme, Achim, Rieger, Michael A, Weigle, Bernd, Bachmann, Michael, Rieber, E. Peter
Format: Article
Language:English
Subjects:
Blood Cells
CD8 Antigens
Cell Communication
Cell Line, Tumor
Cytotoxicity, Immunologic
Dendritic Cells - cytology
Dendritic Cells - immunology
Humans
Immunity
Killer Cells, Natural - immunology
Lymphocyte Activation - immunology
Neoplasms - immunology
Neoplasms - pathology
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - physiology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.174.7.4127