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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0023688,
umls-concept:C0026764,
umls-concept:C0030705,
umls-concept:C0032112,
umls-concept:C0185117,
umls-concept:C0442805,
umls-concept:C1171362,
umls-concept:C1515670,
umls-concept:C1540292,
umls-concept:C1552644,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1823153,
umls-concept:C1948023,
umls-concept:C2349976,
umls-concept:C2911684
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pubmed:issue |
1
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pubmed:dateCreated |
2007-6-20
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pubmed:abstractText |
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-gamma and Toll-like receptor (TLR) ligands in isolated MM plasma cells. Blocking the MEK/ERK pathway inhibited IFN-gamma-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-gamma. IFN-gamma-induced STAT1 activation, via MEK/ERK and MyD88/TRAF6, and inhibition of STAT1 reduced B7-H1 expression. MM plasma cells stimulated with IFN-gamma 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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD274,
http://linkedlifedata.com/resource/pubmed/chemical/CD274 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/MYD88 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
110
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
296-304
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17363736-Antigens, CD,
pubmed-meshheading:17363736-Antigens, CD274,
pubmed-meshheading:17363736-Case-Control Studies,
pubmed-meshheading:17363736-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17363736-Humans,
pubmed-meshheading:17363736-Interferon-gamma,
pubmed-meshheading:17363736-Ligands,
pubmed-meshheading:17363736-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:17363736-Multiple Myeloma,
pubmed-meshheading:17363736-Myeloid Differentiation Factor 88,
pubmed-meshheading:17363736-Neoplasm Proteins,
pubmed-meshheading:17363736-Plasma Cells,
pubmed-meshheading:17363736-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:17363736-TNF Receptor-Associated Factor 6,
pubmed-meshheading:17363736-Toll-Like Receptors,
pubmed-meshheading:17363736-Tumor Cells, Cultured,
pubmed-meshheading:17363736-Tumor Escape,
pubmed-meshheading:17363736-Up-Regulation
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pubmed:year |
2007
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pubmed:articleTitle |
Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{gamma} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway.
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pubmed:affiliation |
Institut National de la Santé et de la Recherche Médicale, Unité 837, Institut de Recherche sur le Cancer de Lille, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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