{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:51:15Z","timestamp":1785876675749,"version":"3.56.0"},"reference-count":80,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T00:00:00Z","timestamp":1677801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Lodz","award":["503\/5-061-03\/503-51-001-19-00"],"award-info":[{"award-number":["503\/5-061-03\/503-51-001-19-00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Inflammation is an etiological factor of various chronic diseases contributing to more than 50% of worldwide deaths. In this study, we focus on the immunosuppressive role of the programmed death-1 (PD-1) receptor and its ligand (PD-L1) in inflammatory-related diseases, including chronic rhinosinusitis and head and neck cancers. The study included 304 participants. Of this number, 162 patients had chronic rhinosinusitis with nasal polyps (CRSwNP), 40 patients had head and neck cancer (HNC) and there were 102 healthy subjects. The expression level of the PD-1 and PD-L1 genes in the tissues of the study groups was measured by qPCR and Western blot methods. The associations between the age of the patients and the extent of disease and genes\u2019 expression were evaluated. The study showed a significantly higher mRNA expression of PD-1 and PD-L1 in the tissues of both the CRSwNP and HNC patient groups compared to the healthy group. The severity of CRSwNP significantly correlated with the mRNA expression of PD-1 and PD-L1. Similarly, the age of the NHC patients influenced PD-L1 expression. In addition, a significantly higher level of PD-L1 protein was noticed also for both the CRSwNP and HNC patient groups. The increased expression of PD-1 and PD-L1 may be a potential biomarker of inflammatory-related diseases, including chronic rhinosinusitis and head and neck cancers.<\/jats:p>","DOI":"10.3390\/jcm12052033","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T02:06:43Z","timestamp":1678068403000},"page":"2033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["PD-1 and PD-L1 Expression Levels as a Potential Biomarker of Chronic Rhinosinusitis and Head and Neck Cancers"],"prefix":"10.3390","volume":"12","author":[{"given":"Katarzyna","family":"Malinowska","sequence":"first","affiliation":[{"name":"Department of Allergology and Respiratory Rehabilitation, Medical University of Lodz, 90-725 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3601-1321","authenticated-orcid":false,"given":"Andrzej","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Laryngological Oncology, Audiology and Phoniatrics, Medical University of Lodz, 90-549 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Merecz-Sadowska","sequence":"additional","affiliation":[{"name":"Department of Allergology and Respiratory Rehabilitation, Medical University of Lodz, 90-725 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Paprocka-Zjawiona","sequence":"additional","affiliation":[{"name":"Department of Allergology and Respiratory Rehabilitation, Medical University of Lodz, 90-725 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5495-3550","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Sitarek","sequence":"additional","affiliation":[{"name":"Department of Biology and Pharmaceutical Botany, Medical University of Lodz, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4559-5015","authenticated-orcid":false,"given":"Tomasz","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Zieli\u0144ska-Bli\u017aniewska","sequence":"additional","affiliation":[{"name":"Department of Allergology and Respiratory Rehabilitation, Medical University of Lodz, 90-725 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/ITT.S29834","article-title":"Cancer as an immune-mediated disease","volume":"1","author":"Shurin","year":"2012","journal-title":"Immunotargets Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7403796","DOI":"10.1155\/2019\/7403796","article-title":"Regulation of inflammation in autoimmune disease","volume":"2019","author":"Duan","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_6","first-page":"500","article-title":"Chronic Rhinosinusitis","volume":"96","author":"Sedaghat","year":"2017","journal-title":"Am. Fam. Physician"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.jaci.2018.12.986","article-title":"Prevalence of chronic rhinosinusitis in the general population based on sinus radiology and symptomatology","volume":"143","author":"Lourijsen","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jaci.2013.01.028","article-title":"Genetics of chronic rhinosinusitis: State of the field and directions forward","volume":"131","author":"Hsu","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11882-015-0540-2","article-title":"The Etiology and Pathogenesis of Chronic Rhinosinusitis: A Review of Current Hypotheses","volume":"15","author":"Lam","year":"2015","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.jaci.2022.02.016","article-title":"Mechanisms and pathogenesis of chronic rhinosinusitis","volume":"149","author":"Kato","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/lary.23671","article-title":"Symptoms in chronic rhinosinusitis with and without nasal polyps","volume":"123","author":"Hopkins","year":"2013","journal-title":"Laryngoscope"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1080\/03007995.2020.1815682","article-title":"Systematic literature review of the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyposis","volume":"36","author":"Chen","year":"2020","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11882-009-0031-4","article-title":"Chronic rhinosinusitis with and without nasal polyps: What is the difference?","volume":"9","author":"Huvenne","year":"2009","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/ACI.0000000000000128","article-title":"Risk factors for chronic rhinosinusitis","volume":"15","author":"Min","year":"2015","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2500\/105065892781874829","article-title":"Rhinitis, Sinusitis, and Their Relationships to Allergies","volume":"6","author":"Benninger","year":"1992","journal-title":"Am. J. Rhinol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Han, K.D., Park, S.H., Son, S., Kim, S.H., Kim, I., Kim, J.Y., In, S.M., Kim, Y.S., and Lee, K.I. (2022). Relationship between Chronic Rhinosinusitis and the Incidence of Head and Neck Cancer: A National Population-Based Study. J. Clin. Med., 11.","DOI":"10.3390\/jcm11185316"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"lgz004","DOI":"10.1093\/jncimonographs\/lgz004","article-title":"Chronic Systemic Symptoms in Head and Neck Cancer Patients","volume":"2019","author":"Murphy","year":"2019","journal-title":"JNCI Monogr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_19","unstructured":"WHO International Agency for Research on Cancer (2020). Global Cancer Observatory 2018, World Health Organization."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Almangush, A., De Keukeleire, S., Rottey, S., Ferdinande, L., Vermassen, T., Leivo, I., and M\u00e4kitie, A.A. (2022). Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: Ready for Prime Time?. Cancers, 14.","DOI":"10.3390\/cancers14061558"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1002\/j.1460-2075.1992.tb05481.x","article-title":"Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death","volume":"11","author":"Ishida","year":"1992","journal-title":"EMBO J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1006\/geno.1994.1562","article-title":"Structure and chromosomal localization of the human PD-1 gene (PDCD1)","volume":"23","author":"Shinohara","year":"1994","journal-title":"Genomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3389\/fimmu.2020.00487","article-title":"The Role of PD-1 in Acute and Chronic Infection","volume":"11","author":"Jubel","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1600-065X.2010.00923.x","article-title":"The PD-1 pathway in tolerance and autoimmunity","volume":"236","author":"Francisco","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.3389\/fimmu.2019.02298","article-title":"The Diverse Function of PD-1\/PD-L Pathway Beyond Cancer","volume":"10","author":"Qin","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3389\/fimmu.2016.00550","article-title":"The PD1: PD-L1\/2 pathway from discovery to clinical implementation","volume":"7","author":"Bardhan","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/0161-5890(87)90122-2","article-title":"Antigens of activated rat T lymphocytes including a molecule of 50,000 Mr detected only on CD4 positive T blasts","volume":"24","author":"Paterson","year":"1987","journal-title":"Mol. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Grzywnowicz, M., Zaleska, J., Mertens, D., Tomczak, W., Wlasiuk, P., Kosior, K., Piechnik, A., Bojarska-Junak, A., Dmoszynska, A., and Giannopoulos, K. (2012). Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035178"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"854967","DOI":"10.3389\/fphar.2022.854967","article-title":"PD-1\/PD-L1 Inhibitors in Patients With Preexisting Autoimmune Diseases","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Veluswamy, P., Wacker, M., Scherner, M., and Wippermann, J. (2020). Delicate role of pd-l1\/pd-1 axis in blood vessel inflammatory diseases: Current insight and future significance. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218159"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13077","DOI":"10.1038\/s41598-021-92530-3","article-title":"PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer","volume":"11","author":"Ozawa","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/odi.13088","article-title":"An update of knowledge on PD-L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives","volume":"26","author":"Lenouvel","year":"2020","journal-title":"Oral Dis."},{"key":"ref_33","first-page":"1","article-title":"Prognostic factors, outcomes and staging in ethmoid sinus surgery","volume":"102","author":"Kennedy","year":"1992","journal-title":"Laryngoscope"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s11864-017-0484-y","article-title":"Overview of the 8th Edition TNM Classification for Head and Neck Cancer","volume":"18","author":"Huang","year":"2017","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s11912-019-0799-x","article-title":"Changes in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging of Head and Neck Cancer: Rationale and Implications","volume":"21","author":"Zanoni","year":"2019","journal-title":"Curr. Oncol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Schmittgen","year":"2001","journal-title":"Methods"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"429","DOI":"10.4103\/1947-2714.100998","article-title":"Western blot: Technique, theory, and trouble shooting","volume":"4","author":"Mahmood","year":"2012","journal-title":"N. Am. J. Med. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1177\/147323001003800221","article-title":"T-lymphocyte subpopulations and B7-H1\/PD-1 expression in nasal polyposis","volume":"38","author":"Zhang","year":"2010","journal-title":"J. Int. Med. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1164\/rccm.201402-0234OC","article-title":"Disease-specific T-helper cell polarizing function of lesional dendritic cells in different types of chronic rhinosinusitis with nasal polyps","volume":"190","author":"Shi","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1111\/all.13136","article-title":"Programmed cell death-1 expression correlates with disease severity and IL-5 in chronic rhinosinusitis with nasal polyps","volume":"72","author":"Bobic","year":"2017","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11444","DOI":"10.1038\/s41598-022-15020-0","article-title":"PD-L1 regulates cell proliferation and apoptosis in acute myeloid leukemia by activating PI3K-AKT signaling pathway","volume":"12","author":"Wang","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3389\/fimmu.2020.00467","article-title":"PD-1-Mediated PI3K\/Akt\/mTOR, Caspase 9\/Caspase 3 and ERK Pathways Are Involved in Regulating the Apoptosis and Proliferation of CD4+ and CD8+ T Cells During BVDV Infection in vitro","volume":"11","author":"Liu","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/path.5280","article-title":"MAPK pathway activity plays a key role in PD-L1 expression of lung adenocarcinoma cells","volume":"249","author":"Stutvoet","year":"2019","journal-title":"J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e0166626","DOI":"10.1093\/annonc\/mdw521.048","article-title":"RAS-MAPK signaling is required for the enhanced PD-L1 expression in human lung cancers","volume":"27","author":"Sumimoto","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.3892\/ol.2020.11647","article-title":"PD-L1 expression increased by ifn-\u03b3 via jak2-stat1 signaling and predicts a poor survival in colorectal cancer","volume":"20","author":"Zhao","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.3892\/or.2017.5399","article-title":"The JAK\/STAT pathway is involved in the upregulation of PD-L1 expression in pancreatic cancer cell lines","volume":"37","author":"Doi","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4047","DOI":"10.1038\/s41388-019-0700-2","article-title":"WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer","volume":"38","author":"Castagnoli","year":"2019","journal-title":"Oncogene"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e20200684","DOI":"10.1084\/jem.20200684","article-title":"\u03b2-Catenin regulates tumor-derived PD-L1","volume":"217","author":"Han","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"584626","DOI":"10.3389\/fimmu.2020.584626","article-title":"Regulation of PD-L1 Expression by NF-\u03baB in Cancer","volume":"11","author":"Antonangeli","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10099","DOI":"10.2147\/OTT.S224053","article-title":"PD-LI expression is regulated by NF-\u03baB during EMT signaling in gastric carcinoma","volume":"12","author":"Xu","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Meliante, P.G., Barbato, C., Zoccali, F., Ralli, M., Greco, A., de Vincentiis, M., Colizza, A., Petrella, C., Ferraguti, G., and Minni, A. (2022). Programmed Cell Death-Ligand 1 in Head and Neck Squamous Cell Carcinoma: Molecular Insights, Preclinical and Clinical Data, and Therapies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315384"},{"key":"ref_52","first-page":"727","article-title":"PD-1\/PD-L1 pathway: Current researches in cancer","volume":"10","author":"Han","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41401-020-0366-x","article-title":"Small molecule inhibitors targeting the PD-1\/PD-L1 signaling pathway","volume":"42","author":"Wu","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"964442","DOI":"10.3389\/fimmu.2022.964442","article-title":"The role of PD-1\/PD-L1 and application of immune-checkpoint inhibitors in human cancers","volume":"13","author":"Tang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"362","DOI":"10.3892\/mmr.2021.12001","article-title":"A combination of PD-1\/PD-L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review)","volume":"23","author":"Kong","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"103679","DOI":"10.1016\/j.critrevonc.2022.103679","article-title":"Immunotherapy for head and neck cancer: Present and future","volume":"174","author":"Fasano","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13045-020-01027-5","article-title":"Regulation of PD-L1 expression in the tumor microenvironment","volume":"14","author":"Yi","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e000150","DOI":"10.1136\/esmoopen-2016-000150","article-title":"Tumour-infiltrating lymphocytes are correlated with higher expression levels of PD-1 and PD-L1 in early breast cancer","volume":"2","author":"Kitano","year":"2017","journal-title":"ESMO Open"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1007\/s00432-019-02915-1","article-title":"Clinical impact of PD-L1 and PD-1 expression in squamous cell cancer of the vulva","volume":"145","author":"Thangarajah","year":"2019","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/jso.23281","article-title":"Increased PD-1 expression on CD4+ and CD8+ T cells is involved in immune evasion in gastric cancer","volume":"107","author":"Saito","year":"2013","journal-title":"J. Surg. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"413","DOI":"10.21037\/tlcr.2019.08.09","article-title":"The association of PD-L1 expression with the efficacy of anti-PD-1\/PD-L1 immunotherapy and survival of non-small cell lung cancer patients: A meta-analysis of randomized controlled trials","volume":"8","author":"Xu","year":"2019","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/pds.5487","article-title":"Very high PD-L1 expression as a prognostic indicator of overall survival among patients with advanced non-small cell lung cancer receiving anti-PD-(L)1 monotherapies in routine practice","volume":"31","author":"Shah","year":"2022","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"127ra37","DOI":"10.1126\/scitranslmed.3003689","article-title":"Colocalization of inflammatory response with B7-H1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape","volume":"4","author":"Taube","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Schmidt, L.H., K\u00fcmmel, A., G\u00f6rlich, D., Mohr, M., Br\u00f6ckling, S., Mikesch, J.H., Gr\u00fcnewald, I., Marra, A., Schultheis, A.M., and Wardelmann, E. (2015). PD-1 and PD-L1 expression in NSCLC indicate a favorable prognosis in defined subgroups. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136023"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1016\/j.ejca.2013.02.015","article-title":"Clinical impact of programmed cell death ligand 1 expression in colorectal cancer","volume":"49","author":"Droeser","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.18632\/oncotarget.6429","article-title":"Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumorinfiltrating lymphocytes in ovarian high grade serous carcinoma","volume":"7","author":"Kunze","year":"2016","journal-title":"Oncotarget"},{"key":"ref_67","first-page":"1626","article-title":"High PD-L1 expression is associated with a favorable prognosis in patients with esophageal squamous cell carcinoma undergoing postoperative adjuvant radiotherapy","volume":"17","author":"Jiang","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/labinvest.2013.130","article-title":"Programmed death ligand-1 expression in non-small cell lung cancer","volume":"94","author":"Velcheti","year":"2014","journal-title":"Lab. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"937","DOI":"10.7150\/jca.27199","article-title":"PD-1 and PD-L1 Expression Predicts Radiosensitivity and Clinical Outcomes in Head and Neck Cancer and is Associated with HPV Infection","volume":"10","author":"Lyu","year":"2019","journal-title":"J. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lin, Y.M., Sung, W.W., Hsieh, M.J., Tsai, S.C., Lai, H.W., Yang, S.M., Shen, K.H., Chen, M.K., Lee, H., and Yeh, K.T. (2015). High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142656"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1002\/hed.25713","article-title":"Upregulation of PD-L1 and PD-L2 in neck node metastases of head and neck squamous cell carcinoma","volume":"41","author":"Moratin","year":"2019","journal-title":"Head Neck"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"52889","DOI":"10.18632\/oncotarget.17547","article-title":"PD-L1: A novel prognostic biomarker in head and neck squamous cell carcinoma","volume":"8","author":"Braun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/ijc.30770","article-title":"The PD-1\/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)","volume":"141","author":"Balermpas","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1158\/1078-0432.CCR-15-1543","article-title":"Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma","volume":"22","author":"Vassilakopoulou","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"77010","DOI":"10.18632\/oncotarget.12776","article-title":"PD-L1 expression in tonsillar cancer is associated with human papillomavirus positivity and improved survival: Implications for anti-PD1 clinical trials","volume":"7","author":"Hong","year":"2016","journal-title":"Oncotarget"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ctrv.2018.02.008","article-title":"Immunotherapy in head and neck cancers: A new challenge for immunologists, pathologists and clinicians","volume":"65","author":"Alt","year":"2018","journal-title":"Cancer Treat. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1177\/1724600819884722","article-title":"Expression of PD-1\/PD-L1 in head and neck squamous cell carcinoma and its clinical significance","volume":"34","author":"Chen","year":"2019","journal-title":"Int. J. Biol. Markers"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"527","DOI":"10.4143\/crt.2015.249","article-title":"Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma","volume":"48","author":"Kim","year":"2016","journal-title":"Cancer Res. Treat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1080\/21645515.2019.1571892","article-title":"PD-1 and PD-L1 in cancer immunotherapy: Clinical implications and future considerations","volume":"15","author":"Jiang","year":"2019","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.csbj.2019.03.006","article-title":"Application of PD-1 Blockade in Cancer Immunotherapy","volume":"17","author":"Wu","year":"2019","journal-title":"Comput. Struct. Biotechnol. 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