PMID- 18208411 OWN - NLM STAT- MEDLINE DCOM- 20080725 LR - 20080505 IS - 0041-1132 (Print) IS - 0041-1132 (Linking) VI - 48 IP - 5 DP - 2008 May TI - Quantitative expression of Toll-like receptor-2, -4, and -9 in dendritic cells generated from blasts of patients with acute myeloid leukemia. PG - 861-70 LID - 10.1111/j.1537-2995.2007.01616.x [doi] AB - 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. FAU - Schmitt, Anita AU - Schmitt A AD - Institute for Clinical Transfusion Medicine and Immunogenetics (IKT) gGmbH Ulm, University of Ulm, Ulm, Germany. FAU - Li, Li AU - Li L FAU - Giannopoulos, Krzysztof AU - Giannopoulos K FAU - Greiner, Jochen AU - Greiner J FAU - Reinhardt, Peter AU - Reinhardt P FAU - Wiesneth, Markus AU - Wiesneth M FAU - Schmitt, Michael AU - Schmitt M LA - eng PT - Journal Article DEP - 20080115 PL - United States TA - Transfusion JT - Transfusion JID - 0417360 RN - 0 (Cancer Vaccines) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Peptidoglycan) RN - 0 (RNA, Messenger) RN - 0 (TLR2 protein, human) RN - 0 (TLR4 protein, human) RN - 0 (TLR9 protein, human) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptor 9) RN - 0 (Toll-Like Receptors) SB - IM MH - Adult MH - Aged MH - Cancer Vaccines MH - Cytokines/metabolism MH - Dendritic Cells/drug effects/*physiology MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Gene Expression Regulation, Leukemic MH - Humans MH - Immunophenotyping MH - Immunotherapy/*methods MH - Leukemia, Myeloid, Acute/immunology/*physiopathology/*therapy MH - Leukocytes, Mononuclear/drug effects/physiology MH - Lipopolysaccharides/pharmacology MH - Male MH - Middle Aged MH - Oligodeoxyribonucleotides/pharmacology MH - Peptidoglycan/pharmacology MH - RNA, Messenger/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Toll-Like Receptor 2/genetics/metabolism MH - Toll-Like Receptor 4/genetics/metabolism MH - Toll-Like Receptor 9/genetics/metabolism MH - Toll-Like Receptors/*genetics/metabolism EDAT- 2008/01/23 09:00 MHDA- 2008/07/26 09:00 CRDT- 2008/01/23 09:00 PHST- 2008/01/23 09:00 [pubmed] PHST- 2008/07/26 09:00 [medline] PHST- 2008/01/23 09:00 [entrez] AID - TRF01616 [pii] AID - 10.1111/j.1537-2995.2007.01616.x [doi] PST - ppublish SO - Transfusion. 2008 May;48(5):861-70. doi: 10.1111/j.1537-2995.2007.01616.x. Epub 2008 Jan 15.