Format

Send to

Choose Destination
PLoS One. 2015 May 7;10(5):e0123340. doi: 10.1371/journal.pone.0123340. eCollection 2015.

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

Author information

1
Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium.
2
Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
3
Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium; Center for Oncological Research, University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.

Abstract

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.

PMID:
25951230
PMCID:
PMC4423923
DOI:
10.1371/journal.pone.0123340
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center