scholarly journals Epstein–Barr Virus LMP1 Induces Soluble PD-L1 in Nasopharyngeal Carcinoma

2021 ◽  
Vol 9 (3) ◽  
pp. 603
Author(s):  
Kina Kase ◽  
Satoru Kondo ◽  
Naohiro Wakisaka ◽  
Hirotomo Dochi ◽  
Harue Mizokami ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Early Stage ◽  
Transmembrane Protein ◽  
Barr Virus ◽  
Lmp1 Expression ◽  
Promising Therapeutic Target ◽  
Associated Malignancy ◽  
Epstein Barr

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated malignancy. The principal oncogene of EBV, latent membrane protein 1 (LMP1), induces the expression of programmed death-ligand 1 (PD-L1), which is an immunosuppressive transmembrane protein and a promising therapeutic target for various malignancies. Recent studies have revealed an association between the level of soluble PD-L1 (sPD-L1) and disease progression. However, the role of sPD-L1 in NPC or its relevance to LMP1 has not been elucidated. This study aimed to examine whether LMP1 induces sPD-L1 in vitro and analyze the clinical relevance of LMP1, PD-L1, and sPD-L1 in NPC patients. Analysis of nasopharyngeal cell lines revealed that LMP1 induces both cellular PD-L1 and sPD-L1. Analysis of biopsy specimens from 32 NPC patients revealed that LMP1 expression was significantly correlated with PD-L1 expression. Finally, the serum sPD-L1 level in NPC patients was higher than that in the controls. Moreover, the sPD-L1 level in the advanced stage was higher than that in the early stage. However, LMP1 expression, PD-L1 expression, and sPD-L1 levels were not associated with prognosis. These results suggest that LMP1 induces both sPD-L1 and PD-L1, which are associated with NPC progression.

The Clinical Significance of IGF-1R and Relationship with Epstein–Barr Virus Markers: LMP1 and EBERs in Tunisian Patients with Nasopharyngeal Carcinoma

2020 ◽  
Vol 129 (10) ◽  
pp. 1011-1019
Author(s):  
Nehla Mokni Baizig ◽  
Ben Ayoub Wided ◽  
Olfa El Amine ◽  
Said Gritli ◽  
Michele ElMay
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Immunohistochemical Method ◽  
Barr Virus ◽  
Lmp1 Expression ◽  
Epstein Barr ◽  
The Relationship

Objectives: Tunisia is in the endemic area of nasopharyngeal carcinoma. Epstein–Barr virus (EBV) based assays have been commonly used as standard markers for screening and monitoring the disease. So, it is very important to find novel factors for the early diagnostic and prognostic evaluation of this cancer. The aim of the study was to evaluate the expression of IGF-1R (Insulin Growth Factor Receptor 1), LMP 1 (Latent Membrane Protein 1) and EBERs (EBV encoded RNAs) in order to determine their correlation with clinicopathologic parameters and survival rates in patients with nasopharyngeal carcinoma (NPC). We also looked for the relationship between these biomarkers. Methods: IGF-1R and LMP1 expression was performed by means of immunohistochemical method and EBERs were detected using in situ hybridization of paraffin embedded tumor tissues of 94 patients with nasopharyngeal carcinoma and 45 non-cancerous nasopharyngeal mucosa samples. Results: Our findings demonstrated that IGF-1R was over expressed in 47.87% of NPC patients and only in 2.22% of controls. Positive LMP1 expression was detected in 56.38% of NPC patients and all NPC patients were positive for the EBV-encoded RNAs staining. A statistically significant positive correlation was observed between IGF-1R expression and the tumor size ( P < .001). Kaplan–Meier survival curves showed that NPC patients with a strong IGF-1R expression level have shorter median and 5-year Overall Survival than those with weak expression rates (100.15 vs 102.68 months, P = .08). In addition, median and 5-year Disease-Free Survival was significantly lower in the LMP1 positive NPC patients than in the LMP1 negative ones (53.38 vs 93.37 months, P = .03). Moreover, LMP1 expression correlated strongly with IGF-1R expression ( P = .018). The relationship between these two biomarkers could influence patient survival. Conclusion: IGF1-R and LMP1 could be valuable prognostic markers in Tunisian NPC patients.

scholarly journals Response of Nasopharyngeal Carcinoma Cells to Epstein-Barr Virus Infection In Vitro

2000 ◽  
Vol 80 (8) ◽  
pp. 1149-1160 ◽  
Author(s):  
Chin-Tarng Lin ◽  
Hsiao-Jung Kao ◽  
Jau-Liang Lin ◽  
Wing-Yee Chan ◽  
Han-Chung Wu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Virus Infection ◽  
Epstein Barr Virus ◽  
Carcinoma Cells ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Epstein Barr ◽  
Barr Virus Infection

scholarly journals Epstein–Barr virus-encoded LMP1 induces a hyperproliferative and inflammatory gene expression programme in cultured keratinocytes

2008 ◽  
Vol 89 (11) ◽  
pp. 2806-2820 ◽  
Author(s):  
Mhairi A. Morris ◽  
Christopher W. Dawson ◽  
Wenbin Wei ◽  
John D. O'Neil ◽  
Suzanne E. Stewart ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Motility ◽  
Epstein Barr Virus ◽  
Terminal Differentiation ◽  
Raft Culture ◽  
Barr Virus ◽  
Lmp1 Expression ◽  
Cellular Pathways ◽  
Epstein Barr

SCC12F cells are a line of keratinocytes that retain the capacity for terminal differentiation in vitro. We showed previously that the Epstein–Barr virus (EBV)-encoded oncogene latent membrane protein 1 (LMP1) altered SCC12F morphology in vitro, downregulated cell–cell-adhesion molecule expression and promoted cell motility. In organotypic raft culture, LMP1-expressing cells failed to stratify and formed poorly organized structures which displayed impaired terminal differentiation. To understand better the mechanism(s) by which LMP1 induces these effects, we generated SCC12F cells in which LMP1 expression is inducible. Following induction, these cells exhibited phenotypic changes similar to those observed previously and allowed us to investigate the effects of LMP1 expression on cellular pathways associated with growth, differentiation and morphology. Using microarrays and a number of confirmatory techniques, we identified sets of differentially expressed genes that are characteristically expressed in inflammatory and hyperproliferative epidermis, including chemokines, cytokines and their receptors, growth factors involved in promoting epithelial cell motility and proliferation and signalling molecules that regulate actin filament reorganization and cell movement. Among the genes whose expression was differentially induced significantly by LMP1, the induction of IL-1β and IL-1α was of particular interest, as many of the LMP1-regulated genes identified are established targets of these cytokines. Our findings suggest that alterations in the IL-1 signalling network may be responsible for many of the changes in host-cell gene expression induced in response to LMP1. Identification of these LMP1-regulated genes helps to define the mechanism(s) by which this oncoprotein influences cellular pathways that regulate terminal differentiation, cell motility and inflammation.

scholarly journals Early Detection of Nasopharyngeal Carcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Keiji Tabuchi ◽  
Masahiro Nakayama ◽  
Bungo Nishimura ◽  
Kentaro Hayashi ◽  
Akira Hara
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Early Detection ◽  
Epstein Barr Virus ◽  
Clinical Presentation ◽  
Southern China ◽  
Squamous Cell Carcinomas ◽  
Treatment Results ◽  
Barr Virus ◽  
Associated Malignancy ◽  
Epstein Barr

Nasopharyngeal carcinoma (NPC) is a unique disease with a clinical presentation, epidemiology, and histopathology differing from other squamous cell carcinomas of the head and neck. NPC is an Epstein-Barr virus-associated malignancy with a marked racial and geographic distribution. Specifically, it is highly prevalent in southern China, Southeast Asia, and the Middle East. To date, most NPC patients have been diagnosed in the advanced stage, but the treatment results for advanced NPC are not satisfactory. This paper provides a brief overview regarding NPC, with the focus on the early detection of initial and recurrent NPC lesions.

scholarly journals An EBV+ lymphoepithelioma-like cholangiocarcinoma in a young woman with chronic hepatitis B

2019 ◽  
Vol 12 (7) ◽  
pp. e229520 ◽  
Author(s):  
Sofia V Gearty ◽  
Ayman Al Jurdi ◽  
Meredith E Pittman ◽  
Renuka Gupta
Keyword(s):  
Chronic Hepatitis ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Systemic Chemotherapy ◽  
Early Stage ◽  
Treatment Options ◽  
Rare Type ◽  
Barr Virus ◽  
Epstein Barr ◽  
Almost All

Epstein-Barr virus (EBV) is implicated in the tumorigenesis of a variety of malignancies, including Burkitt’s lymphoma, Hodgkin’s disease and nasopharyngeal carcinoma (NPC). EBV+ lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare type of intrahepatic cholangiocarcinoma with a distinct pathology and poorly understood treatment options. Morphologically, this neoplasm resembles undifferentiated NPC, a commonly EBV+ tumour with a prominent lymphoid infiltrate. Almost all of the current literature regarding LELCC describes early stage tumours that are treated surgically and achieve good outcomes. In contrast, this report documents a late stage LELCC treated unsuccessfully with systemic chemotherapy.

PO-098: Epstein-Barr Virus Latent Membrane Protein Type 1 (LMP1) Expression in Non Endemic Nasopharyngeal Carcinoma

2013 ◽  
Vol 106 ◽  
pp. S41-S42
Author(s):  
S. Rosales-Pérez ◽  
A. Calva-Espinoza ◽  
A. Daidone ◽  
C.H. Flores-Balcázar ◽  
F. Guedea-Edo ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Membrane Protein ◽  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Barr Virus ◽  
Lmp1 Expression ◽  
Epstein Barr ◽  
Virus Latent Membrane Protein ◽  
Membrane Protein Type

scholarly journals Negative plasma Epstein-Barr virus DNA nasopharyngeal carcinoma in an endemic region and its influence on liquid biopsy screening programmes

2019 ◽  
Vol 121 (8) ◽  
pp. 690-698
Author(s):  
John Malcolm Nicholls ◽  
Victor Ho-Fun Lee ◽  
Sik-Kwan Chan ◽  
Ka-Chun Tsang ◽  
Cheuk-Wai Choi ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Early Stage ◽  
Primary Tumour ◽  
Cancer Specific Survival ◽  
Early Stage Disease ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment

Abstract Background Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA. Methods We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0–20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared. Results Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p < 0.001). Though EBV DNA-negative patients had more early-stage disease (p < 0.001) and smaller volumes of the primary tumour and the positive neck nodes (p < 0.001), they had similar 5-year overall survival and cancer-specific survival to those EBV DNA-positive counterparts by stage. Similar results were also seen when plasma EBV DNA cut-off was set at 0 copy/ml. Conclusions Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions. Clinical trial registration Clinicaltrials.gov Identifier: NCT02476669.

scholarly journals NF-κB Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma

2016 ◽  
Vol 90 (14) ◽  
pp. 6475-6488 ◽  
Author(s):  
Rob J. A. Verhoeven ◽  
Shuang Tong ◽  
Gaohong Zhang ◽  
Jingfeng Zong ◽  
Yixin Chen ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Noncoding Rnas ◽  
Viral Proteins ◽  
Long Noncoding Rnas ◽  
Barr Virus ◽  
Iκb Kinase ◽  
Lmp1 Expression ◽  
Epstein Barr ◽  
Bart Mirnas

ABSTRACTEpstein-Barr virus (EBV) expresses few viral proteins in nasopharyngeal carcinoma (NPC) but high levels of BamHI-A rightward transcripts (BARTs), which include long noncoding RNAs (lncRNAs) and BART microRNAs (miRNAs). It is hypothesized that the mechanism for regulation of BARTs may relate to EBV pathogenesis in NPC. We showed that nuclear factor-κB (NF-κB) activates the BART promoters and modulates the expression of BARTs in EBV-infected NPC cells but that introduction of mutations into the putative NF-κB binding sites abolished activation of BART promoters by NF-κB. Binding of p50 subunits to NF-κB sites in the BART promoters was confirmed in electrophoretic mobility shift assays (EMSA) and further demonstratedin vivousing chromatin immunoprecipitation (ChIP) analysis. Expression of BART miRNAs and lncRNAs correlated with NF-κB activity in EBV-infected epithelial cells, while treatment of EBV-harboring NPC C666-1 cells with aspirin (acetylsalicylic acid [ASA]) and the IκB kinase inhibitor PS-1145 inhibited NF-κB activity, resulting in downregulation of BART expression. Expression of EBV LMP1 activates BART promoters, whereas an LMP1 mutant which cannot induce NF-κB activation does not activate BART promoters, further supporting the idea that expression of BARTs is regulated by NF-κB signaling. Expression of LMP1 is tightly regulated in NPC cells, and this study confirmed that miR-BART5-5p downregulates LMP1 expression, suggesting a feedback loop between BART miRNA and LMP1-mediated NF-κB activation in the NPC setting. These findings provide new insights into the mechanism underlying the deregulation of BARTs in NPC and identify a regulatory loop through which BARTs support EBV latency in NPC.IMPORTANCENasopharyngeal carcinoma (NPC) cells are ubiquitously infected with Epstein-Barr virus (EBV). Notably, EBV expresses very few viral proteins in NPC cells, presumably to avoid triggering an immune response, but high levels of EBV BART miRNAs and lncRNAs which exhibit complex functions associated with EBV pathogenesis. The mechanism for regulation of BARTs is critical for understanding NPC oncogenesis. This study provides multiple lines of evidence to show that expression of BARTs is subject to regulation by NF-κB signaling. EBV LMP1 is a potent activator of NF-κB signaling, and we demonstrate that LMP1 can upregulate expression of BARTs through NF-κB signaling and that BART miRNAs are also able to downregulate LMP1 expression. It appears that aberrant NF-κB signaling and expression of BARTs form an autoregulatory loop for maintaining EBV latency in NPC cells. Further exploration of how targeting NF-κB signaling interrupts EBV latency in NPC cells may reveal new options for NPC treatment.

scholarly journals mSphere of Influence: 3-D Culture Models Influence Studies on Epstein-Barr Virus Molecular Pathogenesis in the Epithelium

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
K. H. Y. Shair
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Three Dimensional ◽  
Molecular Pathogenesis ◽  
Stratified Epithelium ◽  
Barr Virus ◽  
Efficient Replication ◽  
Culture Models ◽  
Epstein Barr

ABSTRACT Kathy Shair works in the field of Epstein-Barr virus (EBV)-associated cancers, with emphasis on nasopharyngeal carcinoma (NPC). In this mSphere of Influence article, she reflects on how the paper “Efficient replication of Epstein-Barr virus in stratified epithelium in vitro” by Temple et al. (R. M. Temple, J. Zhu, L. Budgeon, N. D. Christensen, et al., Proc Natl Acad Sci U S A 111:16544–16549, 2014, https://doi.org/10.1073/pnas.1400818111) has influenced her work on EBV molecular pathogenesis in the nasopharynx by highlighting the importance of using three-dimensional (3-D) culture models to study epithelial infection.

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