دورية أكاديمية
أعرض في EDS

PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma

التفاصيل البيبلوغرافية
العنوان: PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma
المؤلفون: Xi-wen Bi, Hua Wang, Wen-wen Zhang, Jing-hua Wang, Wen-jian Liu, Zhong-jun Xia, Hui-qiang Huang, Wen-qi Jiang, Yu-jing Zhang, Liang Wang
المصدر: Journal of Hematology & Oncology, Vol 9, Iss 1, Pp 1-12 (2016)
بيانات النشر: BMC, 2016.
سنة النشر: 2016
المجموعة: LCC:Diseases of the blood and blood-forming organs
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: Natural killer/T-cell lymphoma, Latent membrane protein 1, Epstein–Barr virus, Programmed cell death receptor 1, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract Background Natural killer/T-cell lymphoma (NKTCL) is an Epstein–Barr virus (EBV)-associated, highly aggressive lymphoma. Treatment outcome remains sub-optimal, especially for advanced-stage or relapsed diseases. Programmed cell death receptor 1 (PD-1) and PD ligand 1 (PD-L1) have become promising therapeutic targets for various malignancies, but their role in the pathogenesis and their interactions with EBV in NKTCL remains to be investigated. Methods Expression of PD-L1 was measured in NK-92 (EBV-negative) and SNK-6 (EBV-positive) cells by western blot, quantitative real-time PCR and enzyme-linked immunosorbent assay, and flow cytometry, respectively. Latent membrane protein 1 (LMP1)-harboring lentiviral vectors were transfected into NK-92 cells to examine the correlation between LMP1 and PD-L1 expression. Proteins in the downstream pathways of LMP1 signaling were measured in NK-92 cells transfected with LMP1-harboring or negative control vectors as well as in SNK-6 cells. PD-L1 expression on tumor specimens and serum concentration of soluble PD-L1 were collected in a retrospective cohort of patients with Ann Arbor stage I~II NKTCL, and their prognostic significance were analyzed. Results Expression of PD-L1 was significantly higher in SNK-6 cells than in NK-92 cells, at both protein and mRNA levels. Expression of PD-L1 was remarkably upregulated in NK-92 cells transfected with LMP1-harboring lentiviral vectors compared with those transfected with negative control vectors. Proteins in the MAPK/NF-κB pathway were upregulated in LMP1-expressing NK-92 cells compared with the negative control. Selective inhibitors of those proteins induced significant downregulation of PD-L1 expression in LMP1-expressing NK-92 cells as well as in SNK-6 cells. Patients with a high concentration of serum soluble PD-L1 (≥3.4 ng/ml) or with a high percentage of PD-L1 expression in tumor specimens (≥38 %) exhibited significantly lower response rate to treatment and remarkably worse survival, compared with their counterparts. A high concentration of serum soluble PD-L1 and a high percentage of PD-L1 expression in tumor specimens were independent adverse prognostic factors among patients with stage I~II NKTCL. Conclusions PD-L1 expression positively correlated LMP1 expression in NKTCL, which was probably mediated by the MAPK/NF-κB pathway. PD-L1 expression in serum and tumor tissues has significant prognostic value for early-stage NKTCL.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1756-8722
Relation: http://link.springer.com/article/10.1186/s13045-016-0341-7; https://doaj.org/toc/1756-8722
DOI: 10.1186/s13045-016-0341-7
URL الوصول: https://doaj.org/article/6d8ba534587b4011b112f1e51a60483f
رقم الأكسشن: edsdoj.6d8ba534587b4011b112f1e51a60483f
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:17568722
DOI:10.1186/s13045-016-0341-7