Interleukin-15 Dendritic Cells Harness NK Cell Cytotoxic Effector Function in a Contact- and IL-15-Dependent Manner

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 s...

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Bibliographic Details
Published in:PloS one 2015-05, Vol.10 (5), p.e0123340-e0123340
Main Authors: Anguille, Sébastien, Van Acker, Heleen H, Van den Bergh, Johan, Willemen, Yannick, Goossens, Herman, Van Tendeloo, Viggo F, Smits, Evelien L, Berneman, Zwi N, Lion, Eva
Format: Article
Language:English
Subjects:
Analysis
Antigens
Cancer
Cancer therapies
Cancer vaccines
CD56 Antigen - metabolism
Cell activation
Cell Communication
Cell culture
Cell Line, Tumor
Clinical trials
Coculture Techniques
Cytokines
Cytokines - metabolism
Cytotoxicity
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Effector cells
Granulocyte-macrophage colony-stimulating factor
Health aspects
Health sciences
Hematology
Hospitals
Humans
Immune system
Immunology
Immunotherapy
Infectious diseases
Interleukin 15
Interleukin 4
Interleukin-15 - metabolism
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Laboratories
Lymphatic system
Lymphocyte Activation
Lymphocyte receptors
Medicine
Monocytes
Natural killer cells
Physiological aspects
T cell receptors
Toll-like receptors
Toxicity
Tumor necrosis factor-TNF
Vaccines
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0123340