IFN-alpha skews monocytes into CD56+-expressing dendritic cells with potent functional activities in vitro and in vivo

C Papewalis, B Jacobs, M Wuttke, E Ullrich, T Baehring, R Fenk, HS Willenberg, S Schinner, M Cohnen, J Seissler, KD Zacharowski, WA Scherbaum, M Schott

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    78 Citations (Scopus)

    Abstract

    The antitumor effect of IFN-alpha is mediated by the activation of CTLs, NK cells, and the generation of highly potent Ag-presenting dendritic cells (IFN-DCs). In this study, we show that IFN-DCs generated in vitro from monocytes express CD56 on their surface, a marker which has been thought to be specific for NK cells. FACS analyses of CD56(+) and CD56(-) IFN-DCs showed a nearly identical pattern for most of the classical DC markers. Importantly, however, only CD56(+) IFN-DCs exhibited cytolytic activity up to 24% that could almost completely be blocked (-81%) after coincubation with anti-TRAIL. Intracytoplasmatic cytokine staining revealed that the majority of IFN-DCs independently of their CD56 expression were IFN-gamma positive as well. In contrast, CD56(+) IFN-DCs showed stronger capacity in stimulating allogenic T cells compared with CD56(-) IFN-DC. Based on these results, five patients with metastasized medullary thyroid carcinoma were treated for the first time with monocyte-derived tumor Ag-pulsed IFN-DCs. After a long term follow-up (in mean 37 mo) all patients are alive. Immunohistochemical analyses of delayed-type hypersensitivity skin reaction showed a strong infiltration with CD8(+) cells. In two patients no substantial change in tumor morphology was detected. Importantly, by analyzing PBMCs, these patients also showed an increase of Ag-specific IFN-gamma-secreting T cells. In summary, we here describe for the first time that cytotoxic activity of IFN-DCs is mainly mediated by an IFN-DC subset showing partial phenotypic and functional characteristics of NK cells. These cells represent another mechanism of the antitumor effect induced by IFN-alpha.
    Translated title of the contributionIFN-alpha skews monocytes into CD56+-expressing dendritic cells with potent functional activities in vitro and in vivo
    Original languageEnglish
    Pages (from-to)1462 - 1470
    Number of pages9
    JournalJournal of Immunology
    Volume180(3)
    Publication statusPublished - Feb 2008

    Bibliographical note

    Publisher: The American Association of Immunologists

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  • Cite this

    Papewalis, C., Jacobs, B., Wuttke, M., Ullrich, E., Baehring, T., Fenk, R., Willenberg, HS., Schinner, S., Cohnen, M., Seissler, J., Zacharowski, KD., Scherbaum, WA., & Schott, M. (2008). IFN-alpha skews monocytes into CD56+-expressing dendritic cells with potent functional activities in vitro and in vivo. Journal of Immunology, 180(3), 1462 - 1470. http://www.jimmunol.org/cgi/content/full/180/3/1462