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Tumoricidal Potential of Native Blood Dendritic Cells: Direct Tumor Cell Killing and Activation of NK Cell-Mediated Cytotoxicity¹

Marc Schmitz^2,*, Senming Zhao^*, Yvonne Deuse^*, Knut Schäkel^*, Rebekka Wehner^*, Hanka Wöhner^*, Kristina Hölig, Florian Wienforth^*, Andrea Kiessling^*, Martin Bornhäuser, Achim Temme^*, Michael A. Rieger^*, Bernd Weigle^*, Michael Bachmann^* and E. Peter Rieber^*

^* Institute of Immunology, Institute of Transfusion Medicine, and Department of Medicine I, Medical Faculty, Technical University of Dresden, Dresden, Germany

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--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- 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- 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.

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