ArticlePloS one2014
CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Viral-driven oncogenesis in T/NK-cell lymphomas: parallels and divergences between HTLV-1 and EBV.International journal of hematology · 2026Review
- Single-cell profiling of HDAC inhibitor-induced EBV lytic heterogeneity defines abortive and refractory states in B lymphoblasts.PLoS pathogens · 2026Article
- Development of a nanoparticle-based immunotherapy targeting CD137 for nasopharyngeal carcinoma treatment.Theranostics · 2026Article
- Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137.Oncoimmunology · 2025Article
- Single-Cell Profiling of HDAC Inhibitor-Induced EBV Lytic Heterogeneity Defines Abortive and Refractory States in B Lymphoblasts.bioRxiv : the preprint server for biology · 2025Article
- Article
- Acute intracranial EBV and CMV infections after chemoimmunotherapy for EBV-associated nasopharyngeal carcinoma: a case report and literature review.Frontiers in oncology · 2025Article
- Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes.Molecular cancer · 2024Review
- Article
- Multiplex spatial analysis reveals increased CD137 expression and m-MDSC neighboring tumor cells in refractory classical Hodgkin Lymphoma.Oncoimmunology · 2024Article
- Novel target and treatment agents for natural killer/T-cell lymphoma.Journal of hematology & oncology · 2023Review
- Epstein-Barr virus-induced ectopic CD137 expression helps nasopharyngeal carcinoma to escape immune surveillance and enables targeting by chimeric antigen receptors.Cancer immunology, immunotherapy : CII · 2022Article
- CD137 costimulation is associated with reduced herpetic stromal keratitis and with developing normal CD8The Journal of general virology · 2022Article
- Immunosuppressive Tumor Microenvironment and Immunotherapy of Epstein-Barr Virus-Associated Malignancies.Viruses · 2022Review
- Antineoplastic and anti-inflammatory effects of bortezomib on systemic chronic active EBV infection.Blood advances · 2021Article
- Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B.World journal of clinical cases · 2021Article
- Review
- Updating targets for natural killer/T-cell lymphoma immunotherapy.Cancer biology & medicine · 2021Review
- Ectopic CD137 expression by rhabdomyosarcoma provides selection advantages but allows immunotherapeutic targeting.Oncoimmunology · 2021Article
- Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To clarify the mechanism for development of Epstein-Barr virus (EBV)-positive T- or NK-cell neoplasms, we focused on the costimulatory receptor CD137. We detected high expression of CD137 gene and its protein on EBV-positive T- or NK-cell lines as compared with EBV-negative cell lines. EBV-positive cells from EBV-positive T- or NK-cell lymphoproliferative disorders (EBV-T/NK-LPDs) patients also had significantly higher CD137 gene expression than control cells from healthy donors. In the presence of IL-2, whose concentration in the serum of EBV-T/NK-LPDs was higher than that of healthy donors, CD137 protein expression was upregulated in the patients' cells whereas not in control cells from healthy donors. In vitro EBV infection of MOLT4 cells resulted in induction of endogenous CD137 expression. Transient expression of LMP1, which was enhanced by IL-2 in EBV-T/NK-LPDs cells, induced endogenous CD137 gene expression in T and NK-cell lines. In order to examine in vivo CD137 expression, we used EBV-T/NK-LPDs xenograft models generated by intravenous injection of patients' cells. We identified EBV-positive and CD8-positive T cells, as well as CD137 ligand-positive cells, in their tissue lesions. In addition, we detected CD137 expression on the EBV infected cells from the lesions of the models by immune-fluorescent staining. Finally, CD137 stimulation suppressed etoposide-induced cell death not only in the EBV-positive T- or NK-cell lines, but also in the patients' cells. These results indicate that upregulation of CD137 expression through LMP1 by EBV promotes cell survival in T or NK cells leading to development of EBV-positive T/NK-cell neoplasms.
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