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Title
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Interleukin-15 dendritic cells harness NK cell cytotoxic effector function in a contact- and IL-15-dependent manner
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Author
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Abstract
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| The contribution of natural killer (NK) cells to the treatment efficacy of dendritic cell (DC)-based cancer vaccines is being increasingly recognized. Much current efforts to optimize this form of immunotherapy are therefore geared towards harnessing the NK cell-stimulatory ability of DCs. In this study, we investigated whether generation of human monocyte-derived DCs with interleukin (IL)-15 followed by activation with a Toll-like receptor stimulus endows these DCs, commonly referred to as IL-15 DCs, with the capacity to stimulate NK cells. In a head-to-head comparison with IL-4 DCs used routinely for clinical studies, IL-15 DCs were found to induce a more activated, cytotoxic effector phenotype in NK cells, in particular in the CD56bright NK cell subset. With the exception of GM-CSF, no significant enhancement of cytokine/chemokine secretion was observed following co-culture of NK cells with IL-15 DCs. IL-15 DCs, but not IL-4 DCs, promoted NK cell tumoricidal activity towards both NK-sensitive and NK-resistant targets. This effect was found to require cell-to-cell contact and to be mediated by DC surface-bound IL-15. This study shows that DCs can express a membrane-bound form of IL-15 through which they enhance NK cell cytotoxic function. The observed lack of membrane-bound IL-15 on gold-standard IL-4 DCs and their consequent inability to effectively promote NK cell cytotoxicity may have important implications for the future design of DC-based cancer vaccine studies. |
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Language
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English
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Source (journal)
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PLoS ONE
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Publication
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2015
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ISSN
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1932-6203
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DOI
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10.1371/JOURNAL.PONE.0123340
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Volume/pages
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10
:5
(2015)
, 18 p.
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Article Reference
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e0123340
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ISI
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000354214400006
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Pubmed ID
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25951230
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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