{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:21:43Z","timestamp":1790515303654,"version":"4.1.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Programmed death-1 (PD-1) is an immunosuppressive receptor functionally bound with programmed death-ligand 1 (PD-L1), which has been reported in various malignancies. However, only a few studies are available for the clinical significance of PD-1\/PD-L1 in nasopharyngeal carcinoma (NPC). In this study, we aim to investigate alterations in PD-1\/PD-L1 by using immunohistochemistry analysis in a cohort of consecutively enrolled NPC patients (n\u2009=\u200999). To further analyse the correlation between PD-1\/PD-L1 and factors involved in clinico-pathology, haematologic biomarkers, EBV-DNA load and outcomes, we collected clinical data for statistical analysis. We observed that lower haemoglobin (HB) and Body Mass Index (BMI) levels were associated with high levels of PD-L1 staining in NPC patients. Importantly, our results suggested that PD-L1 might be a negative indicator for NPC patients. In contrast, a correlation between the PD-1\/PD-L1 level and EBV load was not identified. Moreover, PD-1 positivity was suggested to not be significantly correlated with clinical outcomes. Taken together, our results revealed that PD-L1 might be a potential prognostic biomarker for NPC patients. However, further studies are needed to clarify the underlying mechanism of EBV status in the immunosuppression process induced by the PD-1\/PD-L1 axis.<\/jats:p>","DOI":"10.1038\/srep43627","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T11:58:30Z","timestamp":1488542310000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load"],"prefix":"10.1038","volume":"7","author":[{"given":"Yajuan","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingbo","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiewei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuguo","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conghua","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,3]]},"reference":[{"key":"BFsrep43627_CR1","first-page":"224","volume":"23","author":"A Strazzulla","year":"2015","unstructured":"Strazzulla, A. et al. Nasopharyngeal carcinoma: review of the literature with a focus on therapeutical implications. Infez Med. 23, 224\u2013229 (2015).","journal-title":"Infez Med"},{"key":"BFsrep43627_CR2","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.radonc.2013.10.020","volume":"110","author":"X Sun","year":"2014","unstructured":"Sun, X. et al. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol. 110, 398\u2013403 (2014).","journal-title":"Radiother Oncol"},{"key":"BFsrep43627_CR3","doi-asserted-by":"crossref","first-page":"24511","DOI":"10.18632\/oncotarget.4312","volume":"6","author":"AC Li","year":"2015","unstructured":"Li, A. C. et al. Distant metastasis risk and patterns of nasopharyngeal carcinoma in the era of IMRT: long-term results and benefits of chemotherapy. Oncotarget. 6, 24511\u201324521 (2015).","journal-title":"Oncotarget"},{"key":"BFsrep43627_CR4","first-page":"310","volume":"58","author":"R Khanna","year":"1998","unstructured":"Khanna, R. et al. Molecular characterization of antigen-processing function in nasopharyngeal carcinoma (NPC): evidence for efficient presentation of Epstein-Barr virus cytotoxic T-cell epitopes by NPC cells. Cancer Res. 58, 310\u2013314 (1998).","journal-title":"Cancer Res"},{"key":"BFsrep43627_CR5","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/sj.icb.7100046","volume":"85","author":"S Pai","year":"2007","unstructured":"Pai, S. et al. Nasopharyngeal carcinoma-associated Epstein-Barr virus-encoded oncogene latent membrane protein 1 potentiates regulatory T-cell function. Immunol Cell Biol. 85, 370\u2013377 (2007).","journal-title":"Immunol Cell Biol"},{"key":"BFsrep43627_CR6","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/ni.1790","volume":"10","author":"BT Fife","year":"2009","unstructured":"Fife, B. T. et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol. 10, 1185\u20131192 (2009).","journal-title":"Nat Immunol"},{"key":"BFsrep43627_CR7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.immunol.20.091101.091806","volume":"20","author":"BM Carreno","year":"2002","unstructured":"Carreno, B. M. & Collins, M. The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. Annu Rev Immunol. 20, 29\u201353 (2002).","journal-title":"Annu Rev Immunol"},{"key":"BFsrep43627_CR8","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s10549-013-2581-3","volume":"139","author":"S Muenst","year":"2013","unstructured":"Muenst, S. et al. The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 139, 667\u2013676 (2013).","journal-title":"Breast Cancer Res Treat"},{"key":"BFsrep43627_CR9","doi-asserted-by":"crossref","first-page":"e82870","DOI":"10.1371\/journal.pone.0082870","volume":"8","author":"JR Kim","year":"2013","unstructured":"Kim, J. R. et al. Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas. Plos One 8, e82870 (2013).","journal-title":"Plos One"},{"key":"BFsrep43627_CR10","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cell.2015.08.052","volume":"162","author":"S Kleffel","year":"2015","unstructured":"Kleffel, S. et al. Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth. Cell. 162, 242\u20131256 (2015).","journal-title":"Cell"},{"key":"BFsrep43627_CR11","first-page":"14595","volume":"8","author":"F Xu","year":"2015","unstructured":"Xu, F. et al. Clinicopathological and prognostic value of programmed death ligand-1 (PD-L1) in renal cell carcinoma: a metaanalysis. Int J Clin Exp Med. 8, 14595\u201314603 (2015).","journal-title":"Int J Clin Exp Med"},{"key":"BFsrep43627_CR12","doi-asserted-by":"crossref","first-page":"e281","DOI":"10.1038\/bcj.2015.1","volume":"5","author":"ZZ Yang","year":"2015","unstructured":"Yang, Z. Z. et al. PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer J. 5, e281 (2015).","journal-title":"Blood Cancer J"},{"key":"BFsrep43627_CR13","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1158\/0008-5472.CAN-12-2606","volume":"73","author":"C Badoual","year":"2013","unstructured":"Badoual, C. et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res. 73, 128\u2013138 (2013).","journal-title":"Cancer Res"},{"key":"BFsrep43627_CR14","first-page":"e136023","volume":"10","author":"LH Schmidt","year":"2015","unstructured":"Schmidt, L. H. et al. PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. Plos One 10, e136023 (2015).","journal-title":"Plos One"},{"key":"BFsrep43627_CR15","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.humpath.2015.09.006","volume":"47","author":"MZ Baptista","year":"2016","unstructured":"Baptista, M. Z., Sarian, L. O., Derchain, S. F., Pinto, G. A. & Vassallo, J. Prognostic significance of PD-L1 and PD-L2 in breast cancer. Hum Pathol. 47, 78\u201384 (2016).","journal-title":"Hum Pathol"},{"key":"BFsrep43627_CR16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s12032-015-0501-6","volume":"32","author":"J Zhang","year":"2015","unstructured":"Zhang, J. et al. Co-expression of PD-1 and PD-L1 predicts poor outcome in nasopharyngeal carcinoma. Med Oncol. 32, 86 (2015).","journal-title":"Med Oncol"},{"key":"BFsrep43627_CR17","first-page":"e157969","volume":"11","author":"VH Lee","year":"2016","unstructured":"Lee, V. H. et al. Correlation of PD-L1 Expression of Tumor Cells with Survival Outcomes after Radical Intensity-Modulated Radiation Therapy for Non-Metastatic Nasopharyngeal Carcinoma. Plos One. 11, e157969 (2016).","journal-title":"Plos One"},{"key":"BFsrep43627_CR18","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1038\/modpathol.2010.130","volume":"23","author":"MC Hsu","year":"2010","unstructured":"Hsu, M. C. et al. Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma. Mod Pathol. 23, 1393\u20131403 (2010).","journal-title":"Mod Pathol"},{"key":"BFsrep43627_CR19","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/nrd3806","volume":"11","author":"A Flemming","year":"2012","unstructured":"Flemming, A. Cancer: PD1 makes waves in anticancer immunotherapy. Nat Rev Drug Discov. 11, 601 (2012).","journal-title":"Nat Rev Drug Discov"},{"key":"BFsrep43627_CR20","doi-asserted-by":"crossref","first-page":"22","DOI":"10.21037\/cco.2016.03.08","volume":"5","author":"A Jain","year":"2016","unstructured":"Jain, A., Chia, W. K. & Toh, H. C. Immunotherapy for nasopharyngeal cancer-a review. Chin Clin Oncol. 5, 22 (2016).","journal-title":"Chin Clin Oncol"},{"key":"BFsrep43627_CR21","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/S0140-6736(16)00587-0","volume":"387","author":"L Fehrenbacher","year":"2016","unstructured":"Fehrenbacher, L. et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 387, 1837\u20131846 (2016).","journal-title":"Lancet"},{"key":"BFsrep43627_CR22","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1517\/14712598.2016.1141195","volume":"16","author":"L Spain","year":"2016","unstructured":"Spain, L. & Larkin, J. Combination immune checkpoint blockade with ipilimumab and nivolumab in the management of advanced melanoma. Expert Opin Biol Ther. 16, 389\u2013396 (2016).","journal-title":"Expert Opin Biol Ther"},{"key":"BFsrep43627_CR23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.phrs.2015.06.011","volume":"99","author":"A Bobbio","year":"2015","unstructured":"Bobbio, A. & Alifano, M. Immune therapy of non-small cell lung cancer. The future. Pharmacol Res. 99, 17\u2013222 (2015).","journal-title":"Pharmacol Res"},{"key":"BFsrep43627_CR24","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/bjc.2014.555","volume":"112","author":"A D\u2019Incecco","year":"2015","unstructured":"D\u2019Incecco, A. et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 112, 95\u2013102 (2015).","journal-title":"Br J Cancer"},{"key":"BFsrep43627_CR25","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1158\/0008-5472.CAN-15-2001","volume":"76","author":"F Concha-Benavente","year":"2016","unstructured":"Concha-Benavente, F. et al. Identification of the Cell-Intrinsic and -Extrinsic Pathways Downstream of EGFR and IFNgamma That Induce PD-L1 Expression in Head and Neck Cancer. Cancer Res. 76, 1031\u20131043 (2016).","journal-title":"Cancer Res"},{"key":"BFsrep43627_CR26","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.immuni.2016.06.001","volume":"44","author":"JM Pitt","year":"2016","unstructured":"Pitt, J. M. et al. Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors. Immunity. 44, 1255\u20131269 (2016).","journal-title":"Immunity"},{"key":"BFsrep43627_CR27","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1158\/1078-0432.CCR-15-2412","volume":"22","author":"A Martens","year":"2016","unstructured":"Martens, A. et al. Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced melanoma Patients Treated with Ipilimumab. Clin Cancer Res. 22, 2908\u20132918 (2016).","journal-title":"Clin Cancer Res"},{"key":"BFsrep43627_CR28","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.1182\/blood-2010-11-317297","volume":"117","author":"T Yamamoto","year":"2011","unstructured":"Yamamoto, T. et al. Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood. 117, 4805\u20134815 (2011).","journal-title":"Blood"},{"key":"BFsrep43627_CR29","doi-asserted-by":"crossref","first-page":"13179","DOI":"10.1038\/srep13179","volume":"5","author":"M Massanella","year":"2015","unstructured":"Massanella, M. et al. Methamphetamine Use in HIV-infected Individuals Affects T-cell Function and Viral Outcome during Suppressive Antiretroviral Therapy. Sci Rep. 5, 13179 (2015).","journal-title":"Sci Rep"},{"key":"BFsrep43627_CR30","doi-asserted-by":"crossref","first-page":"7131","DOI":"10.1128\/JVI.78.13.7131-7137.2004","volume":"78","author":"JM Burrows","year":"2004","unstructured":"Burrows, J. M. et al. Selection pressure-driven evolution of the Epstein-Barr virus-encoded oncogene LMP1 in virus isolates from Southeast Asia. J Virol. 78, 7131\u20137137 (2004).","journal-title":"J Virol"},{"key":"BFsrep43627_CR31","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.oraloncology.2013.12.011","volume":"50","author":"TT Yip","year":"2014","unstructured":"Yip, T. T., Ngan, R. K., Fong, A. H. & Law, S. C. Application of circulating plasma\/serum EBV DNA in the clinical management of nasopharyngeal carcinoma. Oral Oncol. 50, 527\u2013538 (2014).","journal-title":"Oral Oncol"},{"key":"BFsrep43627_CR32","doi-asserted-by":"crossref","first-page":"12189","DOI":"10.18632\/oncotarget.2608","volume":"5","author":"W Fang","year":"2014","unstructured":"Fang, W. et al. EBV-driven LMP1 and IFN-gamma up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy. Oncotarget. 5, 12189\u2013121202 (2014","journal-title":"Oncotarget"},{"key":"BFsrep43627_CR33","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nri1349","volume":"4","author":"L Chen","year":"2004","unstructured":"Chen, L., Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol. 4, 336\u2013347 (2004).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep43627_CR34","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1177\/1078155214538087","volume":"21","author":"J Lu","year":"2015","unstructured":"Lu, J., Lee-Gabel, L., Nadeau, M. C., Ferencz, T. M. & Soefje, S. A. Clinical evaluation of compounds targeting PD-1\/PD-L1 pathway for cancer immunotherapy. J. Oncol Pharm Pract. 21, 451\u2013467 (2015).","journal-title":"J. Oncol Pharm Pract."},{"key":"BFsrep43627_CR35","doi-asserted-by":"crossref","first-page":"e515","DOI":"10.1097\/MD.0000000000000515","volume":"94","author":"Y Zhang","year":"2015","unstructured":"Zhang, Y. et al. Prognostic significance of programmed cell death 1 (PD-1) or PD-1 ligand 1 (PD-L1) Expression in epithelialoriginated cancer: a meta-analysis. Medicine (Baltimore). 94, e515 (2015).","journal-title":"Medicine (Baltimore)"},{"key":"BFsrep43627_CR36","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","volume":"12","author":"DM Pardoll","year":"2012","unstructured":"Pardoll, D. M., The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 12, 252\u2013264 (2012).","journal-title":"Nat Rev Cancer"},{"key":"BFsrep43627_CR37","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1097\/JTO.0000000000000526","volume":"10","author":"KM Kerr","year":"2015","unstructured":"Kerr, K. M. et al. Programmed Death-Ligand 1 Immunohistochemistry in Lung Cancer: In what state is this art? J Thorac Oncol. 10(7), 985\u2013989 (2015).","journal-title":"J Thorac Oncol"},{"key":"BFsrep43627_CR38","doi-asserted-by":"crossref","first-page":"790","DOI":"10.3390\/ijms17050790","volume":"17","author":"G Scognamiglio","year":"2016","unstructured":"Scognamiglio, G. et al. Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types. Int J Mol Sci. 17(5), 790 (2016).","journal-title":"Int J Mol Sci"},{"key":"BFsrep43627_CR39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13000-016-0545-8","volume":"811","author":"MC Rebelatto","year":"2016","unstructured":"Rebelatto, M. C. et al. Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of nonsmall cell lung cancer and head and neck squamous cell carcinoma. Diagn Pathol. 811(1), 95 (2016).","journal-title":"Diagn Pathol"},{"key":"BFsrep43627_CR40","first-page":"5419","volume":"46","author":"DA Budwit-Novotny","year":"1986","unstructured":"Budwit-Novotny, D. A. et al. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res. 46(10), 5419\u20135425 (1986).","journal-title":"Cancer Res"},{"key":"BFsrep43627_CR41","first-page":"743","volume":"4","author":"N Chakravarti","year":"2015","unstructured":"Chakravarti, N. & Prieto, V. G., Predictive factors of activity of anti-programmed death-1\/programmed death ligand-1 drugs: immunohistochemistry analysis. Transl Lung Cancer Res. 4(6), 743\u2013751 (2015).","journal-title":"Transl Lung Cancer Res"},{"key":"BFsrep43627_CR42","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/PPO.0000000000000059","volume":"20","author":"VA Boussiotis","year":"2014","unstructured":"Boussiotis, V. A., Chatterjee, P. & Li, L. Biochemical signaling of PD-1 on T cells and its functional implications. Cancer J. 20, 265\u2013271 (2014).","journal-title":"Cancer J"},{"key":"BFsrep43627_CR43","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nri1349","volume":"4","author":"L Chen","year":"2004","unstructured":"Chen, L., Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol. 4, 336\u2013347 (2004).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep43627_CR44","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s00262-015-1677-5","volume":"64","author":"S Ostrand-Rosenberg","year":"2015","unstructured":"Ostrand-Rosenberg, S., Horn, L. A. & Alvarez, J. A. Novel strategies for inhibiting PD-1 pathway-mediated immune suppression while simultaneously delivering activating signals to tumor-reactive T cells. Cancer Immunol Immunother. 64, 1287\u20131293 (2015).","journal-title":"Cancer Immunol Immunother"},{"key":"BFsrep43627_CR45","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1084\/jem.20130790","volume":"211","author":"Y Xiao","year":"2014","unstructured":"Xiao, Y., et al. RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance. J Exp Med. 211, 943\u2013959 (2014).","journal-title":"J Exp Med"},{"key":"BFsrep43627_CR46","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1093\/annonc\/mdv009","volume":"26","author":"J Bellmunt","year":"2015","unstructured":"Bellmunt, J. et al. Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol. 26, 812\u2013817 (2015).","journal-title":"Ann Oncol"},{"key":"BFsrep43627_CR47","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.humpath.2016.05.012","volume":"55","author":"Z Li","year":"2016","unstructured":"Li, Z. et al. PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer. Hum Pathol. 55, 182\u2013189 (2016).","journal-title":"Hum Pathol"},{"key":"BFsrep43627_CR48","doi-asserted-by":"crossref","first-page":"33019","DOI":"10.18632\/oncotarget.5028","volume":"6","author":"W Fang","year":"2015","unstructured":"Fang, W. et al. PD-L1 is remarkably over-expressed in EBV-associated pulmonary lymphoepithelioma-like carcinoma and related to poor disease-free survival. Oncotarget. 6, 33019\u201333032 (2015).","journal-title":"Oncotarget"},{"key":"BFsrep43627_CR49","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1007\/s00277-015-2403-2","volume":"94","author":"S Paydas","year":"2015","unstructured":"Paydas, S., Bagir, E., Seydaoglu, G., Ercolak, V. & Ergin, M. Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma. Ann Hematol. 94, 1545\u20131552 (2015).","journal-title":"Ann Hematol"},{"key":"BFsrep43627_CR50","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ebiom.2016.05.025","volume":"9","author":"H Hu","year":"2016","unstructured":"Hu, H. et al. Epstein-Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation. EBioMedicine. 9, 148\u2013160 (2016).","journal-title":"EBioMedicine"},{"key":"BFsrep43627_CR51","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/s00066-016-0999-3","volume":"192","author":"P Ghadjar","year":"2016","unstructured":"Ghadjar, P. et al. Haemoglobin and creatinine values as prognostic factors for outcome of concurrent radiochemotherapy in locally advanced head and neck cancers: Secondary results of two European randomized phase III trials (ARO 95-06, SAKK 10\/94). Strahlenther Onkol. 192, 552\u2013560 (2016).","journal-title":"Strahlenther Onkol"},{"key":"BFsrep43627_CR52","doi-asserted-by":"crossref","first-page":"502","DOI":"10.7150\/jca.11403","volume":"6","author":"XX Liang","year":"2015","unstructured":"Liang, X. X. et al. Significant prognostic impact of chemoradiotherapy-induced hemoglobin decrease on treatment outcomes of nasopharyngeal carcinoma. J. Cancer. 6, 502\u2013510 (2015).","journal-title":"J. Cancer"},{"key":"BFsrep43627_CR53","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1158\/0008-5472.CAN-13-0992","volume":"74","author":"IB Barsoum","year":"2014","unstructured":"Barsoum, I. B., Smallwood, C. A., Siemens, D. R. & Graham, C. H. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res. 74, 665\u2013674 (2014).","journal-title":"Cancer Res"},{"key":"BFsrep43627_CR54","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.radonc.2013.08.003","volume":"110","author":"C Chen","year":"2014","unstructured":"Chen, C., Shen, L. J., Li, B. F. Gao, J. & Xia, Y. F. Smoking is a poor prognostic factor for male nasopharyngeal carcinoma treated with radiotherapy. Radiother Oncol. 110, 409\u2013415 (2014).","journal-title":"Radiother Oncol"},{"key":"BFsrep43627_CR55","doi-asserted-by":"crossref","first-page":"22000","DOI":"10.1038\/srep22000","volume":"6","author":"H Peng","year":"2016","unstructured":"Peng, H. et al. Prognostic Impact of Plasma Epstein-Barr Virus DNA in Patients with Nasopharyngeal Carcinoma Treated using Intensity-Modulated Radiation Therapy. Sci Rep. 6, 22000 (2016).","journal-title":"Sci Rep"},{"key":"BFsrep43627_CR56","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.ijrobp.2015.08.003","volume":"93","author":"LT Liu","year":"2015","unstructured":"Liu, L. T. et al. The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol Phys 93, 862 (2015).","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"BFsrep43627_CR57","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.radonc.2012.09.001","volume":"104","author":"R Guo","year":"2012","unstructured":"Guo, R. et al. Is primary tumor volume still a prognostic factor in intensity modulated radiation therapy for nasopharyngeal carcinoma? Radiother Oncol. 104(3), 294\u2013299 (2012).","journal-title":"Radiother Oncol"},{"key":"BFsrep43627_CR58","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/hed.23010","volume":"35","author":"Z Wu","year":"2013","unstructured":"Wu, Z., Zeng, R. F., Su, Y., Gu, M. F. & Huang, S. M. Prognostic significance of tumor volume in patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation therapy. Head Neck. 35(5), 689\u2013694 (2013).","journal-title":"Head Neck."},{"key":"BFsrep43627_CR59","doi-asserted-by":"crossref","first-page":"15252","DOI":"10.18632\/oncotarget.7553","volume":"7","author":"M Kang","year":"2016","unstructured":"Kang, M. et al. A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results of a prospective multicentric clinical study. Oncotarget. 7(12), 15252\u201315261 (2016).","journal-title":"Oncotarget."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep43627.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep43627","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep43627.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T00:23:47Z","timestamp":1671841427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep43627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,3]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,5,2]]}},"alternative-id":["BFsrep43627"],"URL":"https:\/\/doi.org\/10.1038\/srep43627","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,3]]},"assertion":[{"value":"2 September 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43627"}}