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. 2008 May;48(5):861-70.
doi: 10.1111/j.1537-2995.2007.01616.x. Epub 2008 Jan 15.

Quantitative Expression of Toll-like receptor-2, -4, and -9 in Dendritic Cells Generated From Blasts of Patients With Acute Myeloid Leukemia

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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

Anita Schmitt et al. Transfusion. .

Abstract

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)-alpha, 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-alpha 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.

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