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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5054-5063. Prepublished online as a Blood First Edition Paper on March 18, 2008; DOI 10.1182/blood-2007-12-130609. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-12-130609v1 111/10/5054    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Chang, Y.-C. Articles by Hsieh, S.-L. PubMed PubMed Citation Articles by Chang, Y.-C. Articles by Hsieh, S.-L. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Epigenetic control of MHC class II expression in tumor-associated macrophages by decoy receptor 3 Yung-Chi Chang1, Tse-Ching Chen2, Chun-Ting Lee1, Chih-Ya Yang1, Hsei-Wei Wang1, Chao-Ching Wang2, and Shie-Liang Hsieh1,3,4 1 Department and Institute of Microbiology and Immunology, National Yang-Ming University, Taipei; 2 Department of Pathology, Chang Gung Memorial Hospital, Lin-Kou; 3 Genomics Research Center, Academia Sinica, Taipei; and 4 Immunology Research Center, National Yang-Ming University and Taipei Veterans General Hospital, Taipei, Taiwan 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 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 overexpressing 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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