Characterization of the Role of Interferon-producing Killer Dendritic Cells in Antitumor Immunity: Potential Implications for Immunotherapy in Medullary Thyroid Carcinoma

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Dendritic cells (DCs) are highly potent antigen-presenting cells. Very recently, a completely new DC subtype has been described in mice. These cells are distinct from conventional DCs and plasmocytoid DCs with the molecular expression profile of both natural killer (NK) cells and DCs. They are termed as interferon-producing killer DCs (IKDCs) due to their ability to produce substantial amounts of type I interferons and the ability of killing target cells via tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) pathways. According to our preliminary data, DCs generated from monocytes over the IFN¿ pathway express NK cell marker (including TRAIL) and may therefore resemble IKDC-like human cells. Based on these data and the applicant¿s experience in DC immunotherapy in endocrine malignancies, two major objectives will be followed: first, to analyze IFN¿-generated human DCs from normal volunteers in order to identify human IKDCs and to use these cells in in vitro experiments for the treatment of medullary thyroid carcinoma (MTC) and second, to analyze the role of murine IKDCs in MTC bearing immunodeficient mice and transgenic MTC mice following IKDC vaccination. Murine IKDCs will be activated by using different Toll-like receptor ligands and will also be analyzed by their migratory capacity. The results of these studies represent the basis for a future vaccination trial in MTC.