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Blood, 1 July 2007, Vol. 110, No. 1, pp. 296-304. Prepublished online as a Blood First Edition Paper on March 15, 2007; DOI 10.1182/blood-2006-10-051482. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-10-051482v1 110/1/296    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 Liu, J. Articles by Quesnel, B. Search for Related Content PubMed PubMed Citation Articles by Liu, J. Articles by Quesnel, B. Related Collections Immunobiology Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN- and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway Jizhong Liu1,2, Abdelbasset Hamrouni1,2, Darius Wolowiec3, Valérie Coiteux4, Kazimierz Kuliczkowski3, Dominique Hetuin1,2, Aurore Saudemont1,2, and Bruno Quesnel1,2,4 1 Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 837, Institut de Recherche sur le Cancer de Lille, France; 2 Université de Lille 2, Institut Fédératif de Recherche, France; 3 Department of Hematology, Wroclaw Medical University, Poland; 4 Service des Maladies du Sang, Centre Hospitalier et Universitaire de Lille, France Multiple myeloma (MM) cells inhibit certain T-cell functions. We examined the expression of B7-H1 (PD-L1), a B7-related protein that inhibits T-cell responses, in CD138-purified plasma cells isolated from MM patients, monoclonal gammopathy of undetermined significance patients, and healthy donors. We observed that B7-H1 was expressed in most MM plasma cells, but not cells isolated from monoclonal gammopathy of undetermined significance or healthy donors. This expression was increased or induced by IFN- and Toll-like receptor (TLR) ligands in isolated MM plasma cells. Blocking the MEK/ERK pathway inhibited IFN-–mediated and TLR-mediated expression of B7-H1. Inhibition of the MyD88 and TRAF6 adaptor proteins of the TLR pathway blocked not only B7-H1 expression induced by TLR ligands but also that mediated by IFN-. IFN-–induced STAT1 activation, via MEK/ERK and MyD88/TRAF6, and inhibition of STAT1 reduced B7-H1 expression. MM plasma cells stimulated with IFN- or TLR ligands inhibited cytotoxic T lymphocytes (CTLs) generation and this immunosuppressive effect was inhibited by preincubation with an anti-B7-H1 antibody, the UO126 MEK inhibitor, or by transfection of a dominant-negative mutant of MyD88. Thus, B7-H1 expression by MM cells represents a possible immune escape mechanism that could be targeted therapeutically through inhibition of MyD88/TRAF6 and MEK/ERK/STAT1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D.-M. Kuang, Q. Zhao, C. Peng, J. Xu, J.-P. Zhang, C. Wu, and L. Zheng Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1 J. Exp. Med., June 8, 2009; 206(6): 1327 - 1337. [Abstract] [Full Text] [PDF] M. Rafei, P. M. Campeau, A. Aguilar-Mahecha, M. Buchanan, P. Williams, E. Birman, S. Yuan, Y. K. Young, M.-N. Boivin, K. Forner, et al. Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Inhibiting CD4 Th17 T Cells in a CC Chemokine Ligand 2-Dependent Manner J. Immunol., May 15, 2009; 182(10): 5994 - 6002. [Abstract] [Full Text] [PDF] D. Chiron, C. Pellat-Deceunynck, M. Amiot, R. Bataille, and G. Jego TLR3 Ligand Induces NF-{kappa}B Activation and Various Fates of Multiple Myeloma Cells Depending on IFN-{alpha} Production J. Immunol., April 1, 2009; 182(7): 4471 - 4478. [Abstract] [Full Text] [PDF] M. Marzec, Q. Zhang, A. Goradia, P. N. Raghunath, X. Liu, M. Paessler, H. Y. Wang, M. Wysocka, M. Cheng, B. A. Ruggeri, et al. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1) PNAS, December 30, 2008; 105(52): 20852 - 20857. [Abstract] [Full Text] [PDF] M. Lafon, F. Megret, S. G. Meuth, O. Simon, M. L. Velandia Romero, M. Lafage, L. Chen, L. Alexopoulou, R. A. Flavell, C. Prehaud, et al. Detrimental Contribution of the Immuno-Inhibitor B7-H1 to Rabies Virus Encephalitis J. Immunol., June 1, 2008; 180(11): 7506 - 7515. [Abstract] [Full Text] [PDF] B. Quesnel MEK inhibitor: the MM magic bullet? Blood, September 1, 2007; 110(5): 1402 - 1403. [Full Text] [PDF]

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