Abstract
CD137 is a potent co-stimulatory molecule on activated T cells, and its ligand (CD137L) is expressed on antigen presenting cells (APC). Ectopic expression of CD137 has been identified on Hodgkin Reed-Sternberg (HRS) cells, the malignant cells in Hodgkin Lymphoma (HL), and CD137 on HRS cells was found to support growth of HRS cells and escape from immune surveillance. HRS cells are mostly derived from B cells, which poses the question of how B cells acquire ectopic CD137 expression during the transformation process. HL is associated with Epstein-Barr virus (EBV) infection. We show that the EBV latent membrane protein 1 (LMP1) induces expression of CD137 in HRS cell lines. In a HL tissue microarray, 96% of the CD137-positive HL cases stained positive for LMP1. LMP1 utilizes the PI3K-AKT-mTOR pathway for inducing CD137 expression. These findings support the role of EBV in HL pathogenesis.
Keywords:
CD137; EBV; Hodgkin lymphoma; LMP1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Cell Proliferation
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Gene Expression Regulation, Neoplastic*
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Hodgkin Disease / genetics
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Hodgkin Disease / metabolism
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Hodgkin Disease / pathology*
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Humans
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism*
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Prognosis
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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Reed-Sternberg Cells
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism*
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Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics
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Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism*
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / metabolism*
Substances
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EBV-associated membrane antigen, Epstein-Barr virus
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TNFRSF9 protein, human
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Viral Matrix Proteins
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases