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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 16, 2006 Accepted March 6, 2007 Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression following stimulation with IFN- and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway Jizhong Liu, Abdelbasset Hamrouni, Darius Wolowiec, Valerie Coiteux, Kazimierz Kuliczkowski, Dominique Hetuin, Aurore Saudemont, and Bruno Quesnel* INSERM, unite 837, Institut de Recherche sur le Cancer de Lille, Lille, France Universite de Lille 2, Institut Federatif de Recherche 114, Lille, France Dept of Hematology, Wroclaw Medical University, Wroclaw, Poland Service des Maladies du Sang, Centre Hospitalier et Universitaire de Lille, Lille, France * Corresponding author; email: brunoquesnel{at}hotmail.com. 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 (MGUS) patients, and healthy donors. We observed that B7-H1 was expressed in most MM plasma cells, but not cells isolated from MGUS or healthy donors. This expression was increased or induced by IFN- and Toll-Like Receptor (TLR) ligands in isolated MM plasma cells. Blocking of the MEK/ERK pathway inhibited IFN-- and TLR-mediated expression of B7-H1. Inhibition of the MyD88 and TRAF6 adaptor proteins of the TLR pathway not only blocked 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 CTLs generation and this immunosuppressive effect was inhibited by pre-incubation 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. Chiron, C. Pellat-Deceunynck, M. Maillasson, R. Bataille, and G. Jego Phosphorothioate-Modified TLR9 Ligands Protect Cancer Cells against TRAIL-Induced Apoptosis J. Immunol., October 1, 2009; 183(7): 4371 - 4377. [Abstract] [Full Text] [PDF] L. Zhang, T. F. Gajewski, and J. Kline PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model Blood, August 20, 2009; 114(8): 1545 - 1552. 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