PMID- 23852664
OWN - NLM
STAT- MEDLINE
DCOM- 20150527
LR  - 20211021
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 9
IP  - 3
DP  - 2014 Sep
TI  - In vitro induction of potent tumor-specific cytotoxic T lymphocytes using TLR 
      agonist-activated AML-DC.
PG  - 225-37
LID - 10.1007/s11523-013-0285-6 [doi]
AB  - Dendritic cells (DCs) are recognized as key regulators of the immune system. 
      Active DC immunization protocols are quickly obtaining interest as an alternative 
      therapeutic approach in acute myeloid leukemia patients. Despite apparent 
      progress in DC-based immunotherapy, some discrepancies were reported in 
      generating potent DCs and their source. In addition to monocytes, DCs can be 
      differentiated from leukemic blasts of acute myeloid leukemia (AML) patients 
      (AML-DC) possessing the ability of stimulating anti-leukemic immune response. In 
      this study, we differentiated peripheral blood blasts of 16 out of 20 AML 
      patients in vitro in the presence of GM-CSF and IL-4 into immature AML-DC. Then, 
      DCs matured using different combinations of Toll-like receptor (TLR) ligands to 
      obtain functional DCs as demonstrated by cell morphology, immunophenotype, and 
      functional activity. Autologous cytotoxic T cell induction of matured DCs was 
      evaluated in four patients and compared with immature counterparts. Our results 
      showed that although the TLR3 agonist (Poly I:C) has a synergistic effect on the 
      TLR4 agonist (lipopolysaccharide, LPS), the addition of the TLR7/8 agonist (R848) 
      is necessary to reinforce the effect of LPS or LPS + POLY(I:C) to produce 
      efficient DCs with the higher level of IL-12 (30 to 90 times). Such DCs activate 
      allogeneic T cells and effectively prime autologous cytotoxic T cells in vitro. 
      In contrast, FSL-1 as a TLR2/6 agonist has a negative effect on LPS + Poly(I:C) 
      and LPS + R848 to produce IL-12. Thus, DCs prepared using a maturation mixture 
      including a TLR7/8 agonist may be used as a potential tool for DC-based 
      immunotherapy purposes in leukemic patients.
FAU - Nourizadeh, Maryam
AU  - Nourizadeh M
AD  - Immunology Department, School of Medicine, Tehran University of Medical Sciences, 
      Poorsina Ave., 16 Azar St., Keshavarz Blvd., P.O. Box: 14155-6447, Tehran, 
      Islamic Republic of Iran.
FAU - Masoumi, Farimah
AU  - Masoumi F
FAU - Memarian, Ali
AU  - Memarian A
FAU - Alimoghaddam, Kamran
AU  - Alimoghaddam K
FAU - Moazzeni, Seyed Mohammad
AU  - Moazzeni SM
FAU - Yaghmaie, Marjan
AU  - Yaghmaie M
FAU - Hadjati, Jamshid
AU  - Hadjati J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130714
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (IL4 protein, human)
RN  - 0 (Imidazoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Toll-Like Receptors)
RN  - 207137-56-2 (Interleukin-4)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - O84C90HH2L (Poly I-C)
RN  - V3DMU7PVXF (resiquimod)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Cell Differentiation/drug effects/immunology
MH  - Dendritic Cells/*drug effects/*immunology
MH  - Drug Synergism
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Immunophenotyping
MH  - Immunotherapy, Adoptive/methods
MH  - Interleukin-4/pharmacology
MH  - Leukemia, Myeloid, Acute/blood/*immunology/therapy
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Poly I-C/pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - T-Lymphocytes, Cytotoxic/*drug effects/*immunology
MH  - Toll-Like Receptors/*agonists/immunology
MH  - Young Adult
EDAT- 2013/07/16 06:00
MHDA- 2015/05/28 06:00
CRDT- 2013/07/16 06:00
PHST- 2012/11/11 00:00 [received]
PHST- 2013/06/21 00:00 [accepted]
PHST- 2013/07/16 06:00 [entrez]
PHST- 2013/07/16 06:00 [pubmed]
PHST- 2015/05/28 06:00 [medline]
AID - 10.1007/s11523-013-0285-6 [doi]
PST - ppublish
SO  - Target Oncol. 2014 Sep;9(3):225-37. doi: 10.1007/s11523-013-0285-6. Epub 2013 Jul 
      14.