ArrayExpress Uploaderarrayexpress_sid2800DcR3DcR3hlgG1hlgG104Decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily and is up-regulated in tumors that originate from a diversity of...18349319E-GEOD-10856/profile/8773/arrayexpressuploader14cancercellclassdendriticmacrophagepancreatic cancerDec.12, 2014FalseE-GEOD-10856_A-AFFY-44transcription-profiling-by-array-of-human-monocyteTranscription profiling by array of human monocytes were cultured with DcR3 in the presence of M-CSFSep.02, 2014Decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily and is up-regulated in tumors that originate from a diversity of lineages. DcR3 is capable of promoting angiogenesis, inducing dendritic cell apoptosis, and modulating macrophage differentiation. Since tumor-associated macrophages (TAMs) are the major infiltrating leukocytes in most malignant tumors, we used microarray technology to investigate whether DcR3 contributes to the development of TAMs. Among the DcR3-modulated genes expressed by TAMs, those that encode proteins involved in MHC class II (MHC-II)-dependent antigen presentation were down-regulated substantially, together with the master regulator of MHC-II expression (the class II transactivator, CIITA). The ERK- and JNK-induced deacetylation of histones associated with the CIITA promoters was responsible for DcR3-mediated down-regulation of MHC-II expression. Furthermore, the expression level of DcR3 in cancer cells correlated inversely with HLA-DR levels on TAMs and with the overall survival time of pancreatic cancer patients. The role of DcR3 in the development of TAMs was further confirmed using transgenic mice over-expressing DcR3. This elucidates the molecular mechanism of impaired MHC-II-mediated antigen presentation by TAMs, and raises the possibility that subversion of TAM-induced immunosuppression via inhibition of DcR3 expression might represent a target for the design of new therapeutics. Experiment Overall Design: Freshly isolated human monocytes were cultured with DcR3 or control hIgG1 in the presence of M-CSF for 2 days. Data were collected from two independent donorshttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-10856humanhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-10856/samples/