PMID- 23284789
OWN - NLM
STAT- MEDLINE
DCOM- 20130617
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - Interleukin-15-induced CD56(+) myeloid dendritic cells combine potent tumor 
      antigen presentation with direct tumoricidal potential.
PG  - e51851
LID - 10.1371/journal.pone.0051851 [doi]
LID - e51851
AB  - Dendritic cells (DCs) are the quintessential antigen-presenting cells of the 
      human immune system and play a prime role in coordinating innate and adaptive 
      immune responses, explaining the strong and still growing interest in their 
      application for cancer immunotherapy. Much current research in the field of 
      DC-based immunotherapy focuses on optimizing the culture conditions for in vitro 
      DC generation in order to assure that DCs with the best possible immunogenic 
      qualities are being used for immunotherapy. In this context, monocyte-derived DCs 
      that are alternatively induced by interleukin-15 (IL-15 DCs) have attracted 
      recent attention due to their superior immunostimulatory characteristics. In this 
      study, we show that IL-15 DCs, in addition to potent tumor antigen-presenting 
      function, possess tumoricidal potential and thus qualify for the designation of 
      killer DCs. Notwithstanding marked expression of the natural killer (NK) cell 
      marker CD56 on a subset of IL-15 DCs, we found no evidence of a further 
      phenotypic overlap between IL-15 DCs and NK cells. Allostimulation and antigen 
      presentation assays confirmed that IL-15 DCs should be regarded as bona fide 
      myeloid DCs not only from the phenotypic but also from the functional point of 
      view. Concerning their cytotoxic activity, we demonstrate that IL-15 DCs are able 
      to induce apoptotic cell death of the human K562 tumor cell line, while sparing 
      tumor antigen-specific T cells. The cytotoxicity of IL-15 DCs is predominantly 
      mediated by granzyme B and, to a small extent, by tumor necrosis factor-alpha 
      (TNF-alpha)-related apoptosis-inducing ligand (TRAIL) but is independent of perforin, 
      Fas ligand and TNF-alpha. In conclusion, our data provide evidence of a previously 
      unappreciated role for IL-15 in the differentiation of human monocytes towards 
      killer DCs. The observation that IL-15 DCs have killer DC capacity lends further 
      support to their implementation in DC-based immunotherapy protocols.
FAU - Anguille, Sebastien
AU  - Anguille S
AD  - University of Antwerp, Faculty of Medicine and Health Sciences, Vaccine and 
      Infectious Disease Institute (VAXINFECTIO), Laboratory of Experimental 
      Hematology, Antwerp, Belgium. sebastien.anguille@uza.be
FAU - Lion, Eva
AU  - Lion E
FAU - Tel, Jurjen
AU  - Tel J
FAU - de Vries, I Jolanda M
AU  - de Vries IJ
FAU - Coudere, Karen
AU  - Coudere K
FAU - Fromm, Phillip D
AU  - Fromm PD
FAU - Van Tendeloo, Viggo F
AU  - Van Tendeloo VF
FAU - Smits, Evelien L
AU  - Smits EL
FAU - Berneman, Zwi N
AU  - Berneman ZN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121228
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CD56 Antigen)
RN  - 0 (Interleukin-15)
RN  - 0 (NCAM1 protein, human)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - Antigen-Presenting Cells/*immunology
MH  - CD56 Antigen/*immunology
MH  - Cell Differentiation
MH  - Cytotoxicity, Immunologic/*immunology
MH  - Dendritic Cells/cytology/*immunology
MH  - Flow Cytometry
MH  - Granzymes/immunology/metabolism
MH  - Humans
MH  - Interleukin-15/*immunology
MH  - Killer Cells, Natural/immunology
MH  - Monocytes/cytology/immunology
MH  - Myeloid Cells/*immunology
MH  - Neoplasms/*immunology/metabolism/pathology
PMC - PMC3532168
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/04 06:00
MHDA- 2013/06/19 06:00
PMCR- 2012/12/28
CRDT- 2013/01/04 06:00
PHST- 2012/06/27 00:00 [received]
PHST- 2012/11/07 00:00 [accepted]
PHST- 2013/01/04 06:00 [entrez]
PHST- 2013/01/04 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
PHST- 2012/12/28 00:00 [pmc-release]
AID - PONE-D-12-18783 [pii]
AID - 10.1371/journal.pone.0051851 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e51851. doi: 10.1371/journal.pone.0051851. Epub 2012 Dec 28.