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Quantitative expression of Toll‐like receptor‐2, ‐4, and ‐9 in dendritic cells generated from blasts of patients with acute myeloid leukemia
Author(s) -
Schmitt Anita,
Li Li,
Giannopoulos Krzysztof,
Greiner Jochen,
Reinhardt Peter,
Wiesneth Markus,
Schmitt Michael
Publication year - 2008
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2007.01616.x
Subject(s) - cd80 , myeloid leukemia , cd86 , toll like receptor , dendritic cell , immunology , cd40 , proinflammatory cytokine , myeloid , cd14 , antigen , leukemia , immunotherapy , flow cytometry , biology , cancer research , t cell , immune system , innate immune system , inflammation , cytotoxic t cell , biochemistry , in vitro
BACKGROUND: Dendritic cells (DCs) generated from leukemic blasts constitute a promising tool in immunotherapy for acute myeloid leukemia patients (AML‐DCs), because AML‐DCs express human leukocyte antigens and costimulatory molecules such as CD40, CD80, and CD86 at a higher level than leukemic blasts. Potentiation of AML‐DC vaccine might become feasible by the addition of adjuvants such as lipopolysaccharides (LPS) or CPG‐rich oligodeoxyribonucleotides binding to Toll‐like receptors (TLR) and inducing a stronger Type 1 T‐cell response. STUDY DESIGN AND METHODS: mRNA and protein expression of TLR‐2, ‐4, and ‐9 were analyzed with quantitative real‐time polymerase chain reaction, Western blot, and flow cytometry for mature monocyte‐derived DCs generated from 14 AML patients versus 14 healthy volunteers (HV‐DCs), and the response of the AML‐ and HV‐DCs to different microbial TLR ligands was determined by enzyme‐linked immunosorbent assay for the proinflammatory cytokines tumor necrosis factor (TNF)‐α, inducible protein (Ip)‐10, and interleukin (IL)‐6. RESULTS: AML‐DCs and HV‐DCs strongly expressed TLR‐2 and TLR‐4, while TLR‐9 was expressed at a lower level in both groups. There was no significant difference in TLR expression between the two groups of AML‐DCs and HV‐DCs. In accordance with the TLR expression levels, DCs generated from both AML patients and HVs responded to the known microbial ligands peptidoglycan (PGN) and lipoteichoic acid for TLR‐2 and LPS as ligand for TLR‐4, by producing TNF‐α and IL‐6. A response to the ODNs 2006 and 2216 binding to TLR‐9 was only detected in AML‐DCs. CONCLUSION: Microbial ligands like ODNs and LPS constitute promising adjuvants for enhancing (AML‐) DC vaccines.