PMID- 22231699
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20201226
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 188
IP  - 4
DP  - 2012 Feb 15
TI  - TRAIL(+) human plasmacytoid dendritic cells kill tumor cells in vitro: mechanisms 
      of imiquimod- and IFN-alpha-mediated antitumor reactivity.
PG  - 1583-91
LID - 10.4049/jimmunol.1102437 [doi]
AB  - Dendritic cells (DCs) not only exhibit the unique capacity to evoke primary 
      immune responses, but may also acquire TLR-triggered cytotoxic activity. We and 
      others have previously shown that TLR7/8- and TLR9-stimulated plasmacytoid DCs 
      (pDCs) isolated from human peripheral blood express the effector molecule TRAIL. 
      The exact mechanisms through which pDCs acquire and elicit their cytotoxic 
      activity are still not clear. We now show that in the absence of costimulators, 
      TRAIL induction on pDCs occurs with agonists to intracellular TLRs only and is 
      accompanied by a phenotypic as well as functional maturation, as evidenced by a 
      comparatively superior MLR stimulatory capacity. pDCs acquired TRAIL in an 
      IFN-alpha/beta-dependent fashion and, notably, TRAIL expression on pDCs could be induced 
      by IFN-alpha stimulation alone. At a functional level, both TLR7/8- (imiquimod [IMQ]) 
      and TLR9-stimulated (CpG2216) pDCs lysed Jurkat T cells in a TRAIL- and cell 
      contact-dependent fashion. More importantly, IFN-alpha-activated pDCs acquired 
      similar cytotoxic properties, independent of TLR stimulation and maturation. Both 
      IMQ- and IFN-alpha-activated pDCs could also lyse certain melanoma cell lines in a 
      TRAIL-dependent fashion. Interestingly, suboptimal doses of IMQ and IFN-alpha 
      exhibited synergistic action, leading to optimal TRAIL expression and melanoma 
      cell lysis by pDCs. Our data imply that tumor immunity in patients receiving 
      adjuvant IMQ and/or IFN-alpha may involve the active participation of cytotoxic pDCs.
FAU - Kalb, Madeleine L
AU  - Kalb ML
AD  - Division of Immunology, Allergy and Infectious Diseases, Department of 
      Dermatology, Medical University of Vienna, Vienna 1090, Austria.
FAU - Glaser, Astrid
AU  - Glaser A
FAU - Stary, Georg
AU  - Stary G
FAU - Koszik, Frieder
AU  - Koszik F
FAU - Stingl, Georg
AU  - Stingl G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120109
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Aminoquinolines)
RN  - 0 (Interferon Inducers)
RN  - 0 (Interferon-alpha)
RN  - 0 (TLR7 protein, human)
RN  - 0 (TLR8 protein, human)
RN  - 0 (TLR9 protein, human)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (Toll-Like Receptor 8)
RN  - 0 (Toll-Like Receptor 9)
RN  - P1QW714R7M (Imiquimod)
SB  - IM
MH  - Aminoquinolines/*pharmacology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/*immunology/metabolism
MH  - Humans
MH  - Imiquimod
MH  - Interferon Inducers/pharmacology
MH  - Interferon-alpha/biosynthesis/*immunology/metabolism
MH  - Jurkat Cells
MH  - Melanoma
MH  - Neoplasms/*immunology
MH  - TNF-Related Apoptosis-Inducing Ligand/biosynthesis/*immunology/metabolism
MH  - Toll-Like Receptor 7/immunology/metabolism
MH  - Toll-Like Receptor 8/immunology/metabolism
MH  - Toll-Like Receptor 9/immunology/metabolism
EDAT- 2012/01/11 06:00
MHDA- 2012/03/27 06:00
CRDT- 2012/01/11 06:00
PHST- 2012/01/11 06:00 [entrez]
PHST- 2012/01/11 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
AID - jimmunol.1102437 [pii]
AID - 10.4049/jimmunol.1102437 [doi]
PST - ppublish
SO  - J Immunol. 2012 Feb 15;188(4):1583-91. doi: 10.4049/jimmunol.1102437. Epub 2012 
      Jan 9.