Transcriptomics

Dataset Information

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Transcription profiling by array of human monocytes were cultured with DcR3 in the presence of M-CSF


ABSTRACT: Decoy 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 donors

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

SUBMITTER: Yung-Chi Chang  

PROVIDER: E-GEOD-10856 | ArrayExpress | 2008-04-05

SECONDARY ACCESSION(S): GSE10856PRJNA107355

REPOSITORIES: GEO, ArrayExpress

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Publications

Epigenetic control of MHC class II expression in tumor-associated macrophages by decoy receptor 3.

Chang Yung-Chi YC   Chen Tse-Ching TC   Lee Chun-Ting CT   Yang Chih-Ya CY   Wang Hsei-Wei HW   Wang Chao-Ching CC   Hsieh Shie-Liang SL  

Blood 20080318 10


Decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily and is up-regulated in tumors originating 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 expr  ...[more]

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