ArticleOncotarget2014
EBV-driven LMP1 and IFN-γ up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy.
2 registry-linked trialsOpen access · diamondAbstract read
In one paragraph
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 256 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
256citing papers in PubMed, 6 pooled it
12.5field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Toripalimab in Combination With Concurrent Chemoradiotherapy for Local-regional Recurrent Nasopharyngeal Carcinoma: a Phase 3, Multicentre, Randomised Controlled Trial
Concurrent Chemoradiotherapy With Toripalimab for Local-regional Recurrent Nasopharyngeal Carcinoma: a Prospective, Single-arm, Phase II Trial
Who cites it
256 citing papers in PubMed, 6 syntheses or guidelines pooled it, 382 citations in OpenAlex.
- The ubiquitin-proteasome system is an important driver of EBV-associated nasopharyngeal carcinoma progression: a meta-analysis of transcriptomic data.Scientific reports · 2026Pooled it
- PD-1/PD-L1 inhibitors for locally advanced nasopharyngeal carcinoma: a systematic review and meta-analysis based on randomized controlled trials.BMC cancer · 2025Pooled it
- Efficacy and safety of first-line treatments for recurrent or metastatic nasopharyngeal carcinoma: a systematic review and network meta-analysis.Frontiers in immunology · 2025Pooled it
- Prognostic Value of Programmed Death Ligand-1 Expression in Solid Tumors Irrespective of Immunotherapy Exposure: A Systematic Review and Meta-Analysis.Molecular diagnosis & therapy · 2022Pooled it
- Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials.Journal for immunotherapy of cancer · 2019Pooled it
- Prognostic value of immune checkpoint molecules in head and neck cancer: a meta-analysis.Aging · 2019Pooled it
- Trial
- Analysis of Plasma Epstein-Barr Virus DNA and Clinical Outcomes to Pembrolizumab or Chemotherapy in Recurrent/Metastatic Nasopharyngeal Cancer in KEYNOTE-122.Cancer medicine · 2026Trial
- Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in recurrent/metastatic nasopharyngeal carcinoma.British journal of cancer · 2025Trial
- Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers.World journal of gastrointestinal oncology · 2024Trial
- Toripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial.Nature communications · 2024Trial
- Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma: a multicenter, single-arm, phase 2 trial (ORIENT-4).Signal transduction and targeted therapy · 2021Trial
- Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study.Journal for immunotherapy of cancer · 2020Trial
- Phase I Study of CC-486 Alone and in Combination with Carboplatin or nab-Paclitaxel in Patients with Relapsed or Refractory Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Trial
- Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- The current role of immunotherapy in treating nasopharyngeal carcinoma.Human vaccines & immunotherapeutics · 2026Review
- Review
- The Molecular and Immunological Landscape in Nasopharyngeal Carcinoma (NPC) Differs by Somatostatin Receptor 2 (SSTR2) Expression.Cancer medicine · 2026Article
- Single-cell sequencing reveals an immunotherapy-relevant IFITM1-marked epithelial interferon state in nasopharyngeal carcinoma.Translational oncology · 2026Article
- Beyond oncogenesis: the unexplored benefits of viruses in cancer immunity.Nature reviews. Cancer · 2026Review
196 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 4 institutions in 1 country.
Wenfeng FangState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Jianwei ZhangDepartment of Oncology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Shaodong HongState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Jianhua ZhanState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Nan ChenDepartment of Oncology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China.
Tao QinState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Yanna TangDepartment of Oncology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China.
Yaxiong ZhangState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Shiyang KangState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Ting ZhouState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Xuan WuState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Wenhua LiangState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Zhihuang HuState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Yuxiang MaState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Yuanyuan ZhaoState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Ying TianState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Yunpeng YangState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Cong XueState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Yue YanState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Xue HouState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Peiyu HuangState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Yan HuangState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Hongyun ZhaoState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Li ZhangState Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China. Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Sun Yat-sen University · CNSun Yat-sen University Cancer Center · CNFifth Affiliated Hospital of Sun Yat-sen University · CNSixth Affiliated Hospital of Sun Yat-sen University · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
PD-L1 expression is a feature of Epstein-Barr virus (EBV) associated malignancies such as nasopharyngeal carcinoma (NPC). Here, we found that EBV-induced latent membrane protein 1 (LMP1) and IFN-γ pathways cooperate to regulate programmed cell death protein 1 ligand (PD-L1). Expression of PD-L1 was higher in EBV positive NPC cell lines compared with EBV negative cell lines. PD-L1 expression could be increased by exogenous and endogenous induction of LMP1 induced PD-L1. In agreement, expression of PD-L1 was suppressed by knocking down LMP1 in EBV positive cell lines. We further demonstrated that LMP1 up-regulated PD-L1 through STAT3, AP-1, and NF-κB pathways. Besides, IFN-γ was independent of but synergetic with LMP1 in up-regulating PD-L1 in NPC. Furthermore, we showed that PD-L1 was associated with worse disease-free survival in NPC patients. These results imply that blocking both the LMP1 oncogenic pathway and PD-1/PD-L1 checkpoints may be a promising therapeutic approach for EBV positive NPC patients.
Indexed as
AdolescentAdultAgedAged, 80 and overB7-H1 AntigenBlotting, WesternCarcinomaDisease-Free SurvivalEnzyme-Linked Immunosorbent AssayEpstein-Barr Virus InfectionsFemaleFlow CytometryFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticGene Expression Regulation, ViralHerpesvirus 4, HumanB7-H1 AntigenCD274 protein, humanEBV-associated membrane antigen, Epstein-Barr virusInterferon-gammaRNA, Small InterferingViral Matrix Proteins
Identifiers
What OpenQuestion holds
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LicenceCC BY
Read underepoch 390
Registered trials
NCT04376866ClinicalTrials.gov
NCT04992988ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.