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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2112-2122. Prepublished online as a Blood First Edition Paper on November 3, 2005; DOI 10.1182/blood-2005-01-0428. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-01-0428v1 107/5/2112    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Biswas, S. K. Articles by Sica, A. Search for Related Content PubMed PubMed Citation Articles by Biswas, S. K. Articles by Sica, A. Related Collections Immunobiology Phagocytes Signal Transduction Gene Expression Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-B and enhanced IRF-3/STAT1 activation) Subhra K. Biswas, Lisa Gangi, Saki Paul, Tiziana Schioppa, Alessandra Saccani, Marina Sironi, Barbara Bottazzi, Andrea Doni, Bronte Vincenzo, Fabio Pasqualini, Luca Vago, Manuela Nebuloni, Alberto Mantovani, and Antonio Sica From the Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; Microarray Research Group, Laboratory of Molecular Technology, National Cancer Institute-Science Applications International Corp (SAIC), Frederick, MD; Centro di Eccellenza per l'Innovazione Diagnostica e Terapeutica, Institute of Pathology, State University of Milan, Milan, Italy; Department of Oncology and Surgical Sciences, Oncology Section, Padua University, Padua, Italy; Institute of Pathology, Department of Clinical Sciences "L. Sacco," University of Milan, Milan, Italy; and Istituto Clinico Humanitas, Rozzano, Milan, Italy. To identify the molecular basis underlying the functions of tumor-associated macrophages (TAMs), we characterized the gene expression profile of TAMs isolated from a murine fibrosarcoma in comparison with peritoneal macrophages (PECs) and myeloid suppressor cells (MSCs), using a cDNA microarray technology. Among the differentially expressed genes, 15 genes relevant to inflammation and immunity were validated by real-time polymerase chain reaction (PCR) and protein production. Resting TAMs showed a characteristic gene expression pattern with higher expression of genes coding for the immunosuppressive cytokine IL-10, phagocytosis-related receptors/molecules (Msr2 and C1q), and inflammatory chemokines (CCL2 and CCL5) as expected, as well as, unexpectedly, IFN-inducible chemokines (CXCL9, CXCL10, CXCL16). Immunohistology confirmed and extended the in vitro analysis by showing that TAMs express M2-associated molecules (eg, IL-10 and MGL1), as well as CCL2, CCL5, CXCL9, CXCL10, and CXCL16, but no appreciable NOS2. Lipopolysaccharide (LPS)-mediated activation of TAMs resulted in defective expression of several proinflammatory cytokines (eg, IL-1, IL-6, TNF-) and chemokines (eg, CCL3), as opposed to a strong up-regulation of immunosuppressive cytokines (IL-10, TGF) and IFN-inducible chemokines (CCL5, CXCL9, CXCL10, CXCL16). Thus, profiling of TAMs from a murine sarcoma revealed unexpected expression of IFN-inducible chemokines, associated with an M2 phenotype (IL-10high, IL-12low), and divergent regulation of the NF-B versus the IRF-3/STAT1 pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Solinas, G. Germano, A. Mantovani, and P. 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