PMID- 20078880
OWN - NLM
STAT- MEDLINE
DCOM- 20100707
LR  - 20211020
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 8
DP  - 2010 Jan 15
TI  - Molecular signatures of maturing dendritic cells: implications for testing the 
      quality of dendritic cell therapies.
PG  - 4
LID - 10.1186/1479-5876-8-4 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) are often produced by granulocyte-macrophage 
      colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) stimulation of 
      monocytes. To improve the effectiveness of DC adoptive immune cancer therapy, 
      many different agents have been used to mature DCs. We analyzed the kinetics of 
      DC maturation by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) 
      induction in order to characterize the usefulness of mature DCs (mDCs) for immune 
      therapy and to identify biomarkers for assessing the quality of mDCs. METHODS: 
      Peripheral blood mononuclear cells were collected from 6 healthy subjects by 
      apheresis, monocytes were isolated by elutriation, and immature DCs (iDCs) were 
      produced by 3 days of culture with GM-CSF and IL-4. The iDCs were sampled after 
      4, 8 and 24 hours in culture with LPS and IFN-gamma and were then assessed by 
      flow cytometry, ELISA, and global gene and microRNA (miRNA) expression analysis. 
      RESULTS: After 24 hours of LPS and IFN-gamma stimulation, DC surface expression 
      of CD80, CD83, CD86, and HLA Class II antigens were up-regulated. Th1 attractant 
      genes such as CXCL9, CXCL10, CXCL11 and CCL5 were up-regulated during maturation 
      but not Treg attractants such as CCL22 and CXCL12. The expression of classical 
      mDC biomarker genes CD83, CCR7, CCL5, CCL8, SOD2, MT2A, OASL, GBP1 and HES4 were 
      up-regulated throughout maturation while MTIB, MTIE, MTIG, MTIH, GADD45A and 
      LAMP3 were only up-regulated late in maturation. The expression of miR-155 was 
      up-regulated 8-fold in mDCs. CONCLUSION: DCs, matured with LPS and IFN-gamma, 
      were characterized by increased levels of Th1 attractants as opposed to Treg 
      attractants and may be particularly effective for adoptive immune cancer therapy.
FAU - Jin, Ping
AU  - Jin P
AD  - Department of Transfusion Medicine, Clinical Center, National Institutes of 
      Health, Bethesda, Maryland, USA. pjin@cc.nih.gov
FAU - Han, Tae Hee
AU  - Han TH
FAU - Ren, Jiaqiang
AU  - Ren J
FAU - Saunders, Stefanie
AU  - Saunders S
FAU - Wang, Ena
AU  - Wang E
FAU - Marincola, Francesco M
AU  - Marincola FM
FAU - Stroncek, David F
AU  - Stroncek DF
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100115
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MicroRNAs)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adoptive Transfer
MH  - Antigens, CD/genetics/immunology
MH  - Biomarkers/metabolism
MH  - Cell Differentiation/*drug effects/immunology
MH  - Cells, Cultured
MH  - Chemokines/genetics/immunology
MH  - Cytokines/genetics/immunology
MH  - *Dendritic Cells/drug effects/immunology/physiology
MH  - Gene Expression Profiling
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/immunology/pharmacology
MH  - Histocompatibility Antigens Class II/genetics/immunology
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Interferon-gamma/immunology/*pharmacology
MH  - Lipopolysaccharides/immunology/*pharmacology
MH  - MicroRNAs/genetics/metabolism
MH  - Microarray Analysis
MH  - Monocytes/drug effects/immunology
MH  - *Neoplasms/immunology/therapy
PMC - PMC2841589
EDAT- 2010/01/19 06:00
MHDA- 2010/07/08 06:00
PMCR- 2010/01/15
CRDT- 2010/01/19 06:00
PHST- 2009/09/02 00:00 [received]
PHST- 2010/01/15 00:00 [accepted]
PHST- 2010/01/19 06:00 [entrez]
PHST- 2010/01/19 06:00 [pubmed]
PHST- 2010/07/08 06:00 [medline]
PHST- 2010/01/15 00:00 [pmc-release]
AID - 1479-5876-8-4 [pii]
AID - 10.1186/1479-5876-8-4 [doi]
PST - epublish
SO  - J Transl Med. 2010 Jan 15;8:4. doi: 10.1186/1479-5876-8-4.