PMID- 18081852 OWN - NLM STAT- MEDLINE DCOM- 20080327 LR - 20080211 IS - 1600-0625 (Electronic) IS - 0906-6705 (Linking) VI - 17 IP - 3 DP - 2008 Mar TI - CD40 ligation during dendritic cell maturation reduces cell death and prevents interleukin-10-induced regression to macrophage-like monocytes. PG - 177-87 AB - Dendritic cells (DCs) have become popular candidates in cancer vaccination because of their crucial role in inducing T-cell responses. However, clinical studies greatly differ in their protocols for generating DCs and the efficacy in treating established tumors needs to be improved. We systematically analyzed DCs maturated by five different protocols for surface markers, the alloproliferative T-cell response, the DC survival after cytokine deprivation, the stability of surface markers under the influence of interleukin-10 (IL-10) and the DC cytokine secretion pattern. Monocyte-derived DCs were maturated by CD40-ligand (CD40-L), unmethylated cytosine-guanosine dinucleotides-oligodinucleotides (CpG-ODN), an inflammatory cytokine cocktail (ICC), a combination of ICC and CD40-L, or ICC, CD40-L and CpG-ODN. A high co-expression of DC maturation and costimulation markers was found after treatment with ICC plus CD40-L (69.3 +/- 9.6% CD83/CD80 double positive staining) and correlated with a significantly increased cell survival, a high expression of the antiapoptotic factor bcl-(XL), a stable CD83(high)/CD14(low) expression under the influence of IL-10, and a strong alloproliferative T-cell response. In conclusion, our data support the use of maturation protocols containing ICC plus CD40-L in order to generate highly mature, phenotypically stable, cell-death resistant, and T-cell stimulatory DCs for clinical application in cancer patients. FAU - Haenssle, Holger AU - Haenssle H AD - Department of Dermatology, Georg-August-University Goettingen, Goettingen, Germany. h.haenssle@med.uni-goettingen.de FAU - Buhl, Timo AU - Buhl T FAU - Knudsen, Susanne AU - Knudsen S FAU - Krueger, Ullrich AU - Krueger U FAU - Rosenberger, Albert AU - Rosenberger A FAU - Reich, Kristian AU - Reich K FAU - Neumann, Christine AU - Neumann C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071213 PL - Denmark TA - Exp Dermatol JT - Experimental dermatology JID - 9301549 RN - 0 (Antigens, CD) RN - 0 (CPG-oligonucleotide) RN - 0 (Cytokines) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (bcl-X Protein) RN - 130068-27-8 (Interleukin-10) RN - 147205-72-9 (CD40 Ligand) SB - IM MH - Antigens, CD/metabolism MH - CD40 Ligand/*pharmacology MH - Cell Culture Techniques/*methods MH - Cell Death/*drug effects MH - Cell Proliferation MH - Cells, Cultured MH - Cytokines/genetics/metabolism/*pharmacology MH - Dendritic Cells/cytology/*drug effects MH - Gene Expression/drug effects MH - Humans MH - Immunophenotyping MH - Interleukin-10/genetics/metabolism/*pharmacology MH - Leukapheresis MH - Monocytes/cytology/metabolism MH - Oligodeoxyribonucleotides/*pharmacology MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - T-Lymphocytes/metabolism MH - bcl-X Protein/metabolism EDAT- 2007/12/18 09:00 MHDA- 2008/03/28 09:00 CRDT- 2007/12/18 09:00 PHST- 2007/12/18 09:00 [pubmed] PHST- 2008/03/28 09:00 [medline] PHST- 2007/12/18 09:00 [entrez] AID - EXD668 [pii] AID - 10.1111/j.1600-0625.2007.00668.x [doi] PST - ppublish SO - Exp Dermatol. 2008 Mar;17(3):177-87. doi: 10.1111/j.1600-0625.2007.00668.x. Epub 2007 Dec 13.