{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:18:29Z","timestamp":1769732309995,"version":"3.49.0"},"reference-count":91,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Council for the Financing of Higher Education (Romania)","award":["2025-F-0364"],"award-info":[{"award-number":["2025-F-0364"]}]},{"name":"National Council for the Financing of Higher Education (Romania)","award":["PN-III-P2-2.1-PED-2021-2115 (620 PED)"],"award-info":[{"award-number":["PN-III-P2-2.1-PED-2021-2115 (620 PED)"]}]},{"name":"Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI, Romania)","award":["2025-F-0364"],"award-info":[{"award-number":["2025-F-0364"]}]},{"name":"Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI, Romania)","award":["PN-III-P2-2.1-PED-2021-2115 (620 PED)"],"award-info":[{"award-number":["PN-III-P2-2.1-PED-2021-2115 (620 PED)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: SARS-CoV-2 immunity is understudied in cancer patients. Here, we monitored natural\/vaccine-induced SARS-CoV-2 immunity in patients with head and neck cancer (HNC) stratified as vaccinated (mRNA\/adenovirus-based vaccines), convalescent, and hybrid immunity. Methods: Plasma\/PBMC samples were collected from 49 patients with HNC and 14 non-oncologic controls recruited between August 2021 and March 2022. Longitudinal follow-up was performed on 25 HNC patients. Plasma antibodies (Abs) against Spike (S1\/S2), receptor-binding domain (RBD), and nucleocapsid (NC) of IgG\/IgA isotypes and 25 cytokines\/chemokines were quantified using MILLIPLEX\u00ae technology. The frequency, phenotype, and isotype of circulating SARS-CoV-2-specific B-cells were studied by flow cytometry using RBD tetramers (Tet++). The proliferation of B-cells and CD4+ and CD8+ T-cells in response to Spike\/NC peptides was monitored by a carboxyfluorescein succinimidyl ester (CFSE) assay. Results: Plasma SARS-CoV-2 S1\/S2\/RBD IgG\/IgA Abs were detected in all HNC participants at enrollment median time since immunization (TSI) 117 days at levels similar to controls and were significantly higher in convalescent\/hybrid versus vaccinated. NC IgG\/IgA Abs were only detected after infection. The frequency of Tet++ B-cells, enriched in the CD27+ memory phenotype and IgG\/IgA isotype, positively correlated with plasma levels of RBD IgG\/IgA Abs and Spike-specific CD4+ T-cell proliferation, regardless of the immunization status and TSI. Spike\/NC-specific B-cell proliferation reached the highest levels in convalescent HNC and was positively correlated with NC IgG Abs, but not with the frequency of Tet++ B-cells. Finally, Tet++ B-cell frequencies remained stable between the two subsequent visits (median TSI: 117 versus 341 days), indicating their ability to persist for a relatively long time. Conclusions: This study monitored SARS-CoV-2 humoral\/cellular immunity in an HNC cohort relative to non-oncologic participants and demonstrates that SARS-CoV-2-specific B-cells persist beyond 11 months post-immunization. These findings have implications for the management of HNC in the context of SARS-CoV-2 infection and other viral infections.<\/jats:p>","DOI":"10.3390\/v17060848","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T14:03:11Z","timestamp":1750082591000},"page":"848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Humoral and Cellular Immune Responses to SARS-CoV-2 in Participants with Head and Neck Cancer"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4045-079X","authenticated-orcid":false,"given":"Luminita","family":"M\u0103rutescu","sequence":"first","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 050663 Bucharest, Romania"},{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandru","family":"Enea","sequence":"additional","affiliation":[{"name":"ENT Department, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Coltea Hospital, Rd District, 030171 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nefeli-Maria","family":"Antoniadis","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Neculae","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9625-8922","authenticated-orcid":false,"given":"Diana Antonia","family":"Costea","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Popa","sequence":"additional","affiliation":[{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Dragu","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 050663 Bucharest, Romania"},{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Codrici","sequence":"additional","affiliation":[{"name":"Biochemistry-Proteomics Department, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania"},{"name":"Cell Biology and Histology Department, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9965-7509","authenticated-orcid":false,"given":"Violeta","family":"Ristoiu","sequence":"additional","affiliation":[{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"},{"name":"Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8093-1750","authenticated-orcid":false,"given":"Bianca","family":"Galateanu","sequence":"additional","affiliation":[{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-9432","authenticated-orcid":false,"given":"Ariana","family":"Hudita","sequence":"additional","affiliation":[{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-1822","authenticated-orcid":false,"given":"Gratiela","family":"Gradisteanu Pircalabioru","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 050663 Bucharest, Romania"},{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelali","family":"Filali-Mouhim","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serban","family":"Vifor Gabriel Bertesteanu","sequence":"additional","affiliation":[{"name":"ENT Department, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Coltea Hospital, Rd District, 030171 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Laz\u0103r","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 050663 Bucharest, Romania"},{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-1857","authenticated-orcid":false,"given":"Carmen","family":"Chifiriuc","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 050663 Bucharest, Romania"},{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raluca","family":"Grigore","sequence":"additional","affiliation":[{"name":"ENT Department, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Coltea Hospital, Rd District, 030171 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1922-5640","authenticated-orcid":false,"given":"Petronela","family":"Ancuta","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, 050663 Bucharest, Romania"},{"name":"Research Institute of University of Bucharest, 050663 Bucharest, Romania"},{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H2X 0A9, Canada"},{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC 6128, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). The species severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol., 5, 536\u2013544.","DOI":"10.1038\/s41564-020-0695-z"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/s41564-021-00931-x","article-title":"How SARS-CoV-2 makes the cut","volume":"6","author":"Hoffmann","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liu, Y., Qu, H.Q., Qu, J., Tian, L., and Hakonarson, H. (2020). Expression Pattern of the SARS-CoV-2 Entry Genes ACE2 and TMPRSS2 in the Respiratory Tract. Viruses, 12.","DOI":"10.20944\/preprints202005.0040.v1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41586-020-2575-3","article-title":"Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2","volume":"585","author":"Hoffmann","year":"2020","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/imr.13089","article-title":"Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines","volume":"310","author":"Sette","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1146\/annurev-immunol-101721-061120","article-title":"T Cell Responses to SARS-CoV-2","volume":"41","author":"Sette","year":"2023","journal-title":"Annu. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.chom.2022.02.003","article-title":"Development of a T cell-based immunodiagnostic system to effectively distinguish SARS-CoV-2 infection and COVID-19 vaccination status","volume":"30","author":"Yu","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.chom.2021.05.010","article-title":"SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19","volume":"29","author":"Grifoni","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100354","DOI":"10.1016\/j.xcrm.2021.100354","article-title":"Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells","volume":"2","author":"Cohen","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1016\/j.immuni.2021.08.001","article-title":"Rapid induction of antigen-specific CD4(+) T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination","volume":"54","author":"Painter","year":"2021","journal-title":"Immunity"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eabf1555","DOI":"10.1126\/scitranslmed.abf1555","article-title":"Enhanced SARS-CoV-2 neutralization by dimeric IgA","volume":"13","author":"Wang","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.it.2021.12.001","article-title":"Natural resistance against infections: Focus on COVID-19","volume":"43","author":"Netea","year":"2022","journal-title":"Trends Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107967","DOI":"10.1016\/j.isci.2023.107967","article-title":"Infants and young children generate more durable antibody responses to SARS-CoV-2 infection than adults","volume":"26","author":"Joshi","year":"2023","journal-title":"iScience"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E7","DOI":"10.1038\/s41586-023-06355-3","article-title":"A second update on mapping the human genetic architecture of COVID-19","volume":"621","author":"Initiative","year":"2023","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41587-021-01037-9","article-title":"Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children","volume":"40","author":"Loske","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.cell.2021.02.029","article-title":"COVID-19 and the human innate immune system","volume":"184","author":"Schultze","year":"2021","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3808","DOI":"10.1200\/JCO.21.02986","article-title":"Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant","volume":"40","author":"Valanparambil","year":"2022","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1200\/JCO.21.02257","article-title":"Determinants of Neutralizing Antibody Response After SARS CoV-2 Vaccination in Patients With Myeloma","volume":"40","author":"Nooka","year":"2022","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1200\/JCO.22.00088","article-title":"Humoral Responses Against SARS-CoV-2 and Variants of Concern After mRNA Vaccines in Patients With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia","volume":"40","author":"Chang","year":"2022","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.molmed.2022.07.006","article-title":"Immunogenicity of SARS-CoV-2 vaccines in patients with cancer","volume":"28","author":"Kakkassery","year":"2022","journal-title":"Trends Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"934","DOI":"10.21873\/invivo.12783","article-title":"Impact of the COVID-19 Pandemic on Treatment and Oncologic Outcomes for Cancer Patients in Romania","volume":"36","author":"Trifanescu","year":"2022","journal-title":"In Vivo"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S1470-2045(20)30096-6","article-title":"Cancer patients in SARS-CoV-2 infection: A nationwide analysis in China","volume":"21","author":"Liang","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1158\/2159-8290.CD-20-0422","article-title":"Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak","volume":"10","author":"Dai","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00277-020-04328-4","article-title":"COVID-19 in cancer patients: Clinical characteristics and outcome-an analysis of the LEOSS registry","volume":"100","author":"Ruthrich","year":"2021","journal-title":"Ann. Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s43018-021-00274-w","article-title":"Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study","volume":"2","author":"Fendler","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.ccell.2021.06.002","article-title":"Seroconversion rates following COVID-19 vaccination among patients with cancer","volume":"39","author":"Thakkar","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2082192","DOI":"10.1080\/21645515.2022.2082192","article-title":"Trends in hospitalization and death rates among patients with head and neck cancer in Spain, 2009 to 2019","volume":"18","year":"2022","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.canep.2018.10.014","article-title":"Incidence and mortality trends in oral and oropharyngeal cancers in China, 2005-2013","volume":"57","author":"Zhang","year":"2018","journal-title":"Cancer Epidemiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"681","DOI":"10.4103\/ijmr.IJMR_149_18","article-title":"Carcinogenicity of smokeless tobacco: Evidence from studies in humans & experimental animals","volume":"148","author":"Warnakulasuriya","year":"2018","journal-title":"Indian J. Med. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1158\/1940-6207.CAPR-13-0262","article-title":"Clinical and biochemical studies support smokeless tobacco\u2019s carcinogenic potential in the human oral cavity","volume":"7","author":"Mallery","year":"2014","journal-title":"Cancer Prev. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.oraloncology.2015.02.101","article-title":"Chemoprevention targets for tobacco-related head and neck cancer: Past lessons and future directions","volume":"51","author":"Sheth","year":"2015","journal-title":"Oral Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Constantin, M., Chifiriuc, M.C., Mihaescu, G., Vrancianu, C.O., Dobre, E.G., Cristian, R.E., Bleotu, C., Bertesteanu, S.V., Grigore, R., and Serban, B. (2023). Implications of oral dysbiosis and HPV infection in head and neck cancer: From molecular and cellular mechanisms to early diagnosis and therapy. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1273516"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ursu, R.G., Danciu, M., Spiridon, I.A., Ridder, R., Rehm, S., Maffini, F., McKay-Chopin, S., Carreira, C., Lucas, E., and Costan, V.V. (2018). Role of mucosal high-risk human papillomavirus types in head and neck cancers in Romania. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199663"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ursu, R.G., Luchian, I., Ghetu, N., Costan, V.V., Stamatin, O., Palade, O.D., Damian, C., Iancu, L.S., and Porumb-Andrese, E. (2021). Emerging Oncogenic Viruses in Head and Neck Cancers from Romanian Patients. Appl. Sci., 11.","DOI":"10.3390\/app11199356"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Liao, W., Liang, H., Liang, Y., Gao, X., Liao, G., Cai, S., Liu, L., and Chen, S. (2024). Factors Associated with IgG\/IgM Levels after SARS-CoV-2 Vaccination in Patients with Head and Neck Cancer. Trop. Med. Infect. Dis., 9.","DOI":"10.3390\/tropicalmed9100234"},{"key":"ref_39","first-page":"e37014","article-title":"Immune Response to SARS-CoV-2 Vaccination in Cancer Patients: A Prospective Study","volume":"15","author":"Caramujo","year":"2023","journal-title":"Cureus"},{"key":"ref_40","unstructured":"Marutescu, L., Enea, A., Antoniadis, N.M., Costea, D.A., Neculae, M., Popa, M., Dragu, E., Codrici, E., Ristoiu, V., and Galateanu, B. Unveiling Humoral and Cellular Immune Responses to SARS-CoV-2 in Head and Neck Cancer: A Comparative Study of Vaccination and Natural Infection in Romania. BioRxiv, Preprint."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S0140-6736(23)02268-7","article-title":"Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): A randomised, phase 2b study","volume":"403","author":"Weber","year":"2024","journal-title":"Lancet"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wiche Salinas, T.R., Zhang, Y., Gosselin, A., Rosario, N.F., El-Far, M., Filali-Mouhim, A., Routy, J.P., Chartrand-Lefebvre, C., Landay, A.L., and Durand, M. (2024). Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection. Cells, 13.","DOI":"10.3390\/cells13020157"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41586-020-2456-9","article-title":"Convergent antibody responses to SARS-CoV-2 in convalescent individuals","volume":"584","author":"Robbiani","year":"2020","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eabf8891","DOI":"10.1126\/sciimmunol.abf8891","article-title":"Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence","volume":"5","author":"Hartley","year":"2020","journal-title":"Sci. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41586-021-03207-w","article-title":"Evolution of antibody immunity to SARS-CoV-2","volume":"591","author":"Gaebler","year":"2021","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"eabg6916","DOI":"10.1126\/sciimmunol.abg6916","article-title":"Prolonged evolution of the human B cell response to SARS-CoV-2 infection","volume":"6","author":"Sakharkar","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41586-021-03324-6","article-title":"mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants","volume":"592","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e149150","DOI":"10.1172\/JCI149150","article-title":"First-dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in subjects who have recovered from COVID-19","volume":"131","author":"Mazzoni","year":"2021","journal-title":"J. Clin. Invest."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Roederer, M. (2002). Compensation in flow cytometry. Current Protocols in Cytometry, Wiley. Chapter 1, Unit 1.14.","DOI":"10.1002\/0471142956.cy0114s22"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.4049\/jimmunol.2001436","article-title":"RALDH Activity Induced by Bacterial\/Fungal Pathogens in CD16(+) Monocyte-Derived Dendritic Cells Boosts HIV Infection and Outgrowth in CD4(+) T Cells","volume":"206","author":"Cattin","year":"2021","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"ref_52","unstructured":"Team, R.C. (2024, June 10). R 4.2.3.: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing: Vienna, Austria. Available online: https:\/\/www.R-project.org."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3730","DOI":"10.25083\/rbl\/27.5\/3730.3745","article-title":"SARS CoV-2 virus and the COVID-19 pandemic worldwide and in Romania. An updated data review","volume":"27","author":"Constantin","year":"2022","journal-title":"Rom Biotechnol. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e20202515","DOI":"10.1084\/jem.20202515","article-title":"Persistent cellular immunity to SARS-CoV-2 infection","volume":"218","author":"Breton","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.immuni.2019.04.011","article-title":"T Follicular Helper Cell Biology: A Decade of Discovery and Diseases","volume":"50","author":"Crotty","year":"2019","journal-title":"Immunity"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1093\/infdis\/jiad353","article-title":"SARS-CoV-2 Hybrid Immunity: The Best of Both Worlds","volume":"228","author":"Lasrado","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S1473-3099(22)00801-5","article-title":"Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: A systematic review and meta-regression","volume":"23","author":"Bobrovitz","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101583","DOI":"10.1016\/j.xcrm.2024.101583","article-title":"SARS-CoV-2 breakthrough infections enhance T cell response magnitude, breadth, and epitope repertoire","volume":"5","author":"Tarke","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/s41571-022-00610-8","article-title":"COVID-19 vaccines in patients with cancer: Immunogenicity, efficacy and safety","volume":"19","author":"Fendler","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41591-021-01643-9","article-title":"A guide to immunotherapy for COVID-19","volume":"28","author":"Pickkers","year":"2022","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"740","DOI":"10.52586\/4984","article-title":"Identification of key factors shaping integrated levels of ACE2 and TMPRSS2 expression in head and neck squamous cell carcinoma","volume":"26","author":"Zheng","year":"2021","journal-title":"Front. Biosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1016\/j.csbj.2020.08.024","article-title":"The SARS-CoV-2 host cell receptor ACE2 correlates positively with immunotherapy response and is a potential protective factor for cancer progression","volume":"18","author":"Zhang","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/s13046-020-01708-6","article-title":"TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients","volume":"39","author":"Sacconi","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"725","DOI":"10.5306\/wjco.v13.i8.725","article-title":"COVID-19 and oral cancer: Critical viewpoint","volume":"13","author":"Gopalakrishnan","year":"2022","journal-title":"World J. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"110089","DOI":"10.1016\/j.mehy.2020.110089","article-title":"EMMPRIN\/BASIGIN as a biological modulator of oral cancer and COVID-19 interaction: Novel propositions","volume":"143","author":"Varadarajan","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Han, B., Sun, M., Zhao, Y., Baranova, A., Cao, H., Liu, S., Shen, X., Hou, L., Fang, J., and Lian, M. (2024). Genetic predisposition to milder forms of COVID-19 may provide some resilience to head and neck cancers. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1384061"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Wang, H., Fang, N., Mozumder, P., Jiang, R., and Wang, X. (2024). Exploring the protective association between COVID-19 infection and laryngeal cancer: Insights from a Mendelian randomization study. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1380982"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1007\/s00405-020-06514-6","article-title":"The impact and prevalence of SARS-CoV-2 in patients with head and neck cancer and acute upper airway infection in a tertiary otorhinolaryngology referral center in Denmark","volume":"278","author":"Andersen","year":"2021","journal-title":"Eur. Arch. Oto-Rhino-Laryngol. Off. J. Eur. Fed. Oto-Rhino-Laryngol. Soc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nri.2016.99","article-title":"Emerging roles of p53 and other tumour-suppressor genes in immune regulation","volume":"16","author":"Mandinova","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1126\/science.abg9175","article-title":"mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection","volume":"372","author":"Stamatatos","year":"2021","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1016\/j.cell.2021.06.021","article-title":"In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies","volume":"184","author":"Li","year":"2021","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1007\/s00262-022-03313-2","article-title":"Inhibition of the CCR6-CCL20 axis prevents regulatory T cell recruitment and sensitizes head and neck squamous cell carcinoma to radiation therapy","volume":"72","author":"Rutihinda","year":"2023","journal-title":"Cancer Immunol. Immunother. CII"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev-immunol-031210-101400","article-title":"Follicular helper CD4 T cells (TFH)","volume":"29","author":"Crotty","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"110117","DOI":"10.1016\/j.isci.2024.110117","article-title":"The alarmin IL-33 exacerbates pulmonary inflammation and immune dysfunction in SARS-CoV-2 infection","volume":"27","author":"Wang","year":"2024","journal-title":"iScience"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1056\/NEJMoa2028700","article-title":"Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia","volume":"384","author":"Rosas","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1056\/NEJMoa2100433","article-title":"Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19","volume":"384","author":"Investigators","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Flisiak, R., Jaroszewicz, J., Rogalska, M., Lapinski, T., Berkan-Kawinska, A., Bolewska, B., Tudrujek-Zdunek, M., Kozielewicz, D., Rorat, M., and Leszczynski, P. (2021). Tocilizumab Improves the Prognosis of COVID-19 in Patients with High IL-6. J. Clin. Med., 10.","DOI":"10.2139\/ssrn.3770003"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.immuni.2022.04.003","article-title":"Analysis of memory B cells identifies conserved neutralizing epitopes on the N-terminal domain of variant SARS-Cov-2 spike proteins","volume":"55","author":"Wang","year":"2022","journal-title":"Immunity"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"eabi6950","DOI":"10.1126\/sciimmunol.abi6950","article-title":"Distinct antibody and memory B cell responses in SARS-CoV-2 na\u00efve and recovered individuals following mRNA vaccination","volume":"6","author":"Goel","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.cell.2021.01.050","article-title":"Maturation and persistence of the anti-SARS-CoV-2 memory B cell response","volume":"184","author":"Sokal","year":"2021","journal-title":"Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"115498","DOI":"10.1016\/j.celrep.2025.115498","article-title":"Long-lasting antibody B-cell responses to SARS-CoV-2 three years after the onset of the pandemic","volume":"44","author":"Rubio","year":"2025","journal-title":"Cell Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1016\/S2666-5247(23)00255-0","article-title":"Durability and cross-reactive immune memory to SARS-CoV-2 in individuals 2 years after recovery from COVID-19: A longitudinal cohort study","volume":"5","author":"Guo","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41577-021-00583-2","article-title":"Mucosal vaccines\u2014Fortifying the frontiers","volume":"22","author":"Lavelle","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41586-025-08910-6","article-title":"Nasal vaccines for respiratory infections","volume":"641","author":"Kiyono","year":"2025","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e202451606","DOI":"10.1002\/eji.202451606","article-title":"Passive Immunization in the Prevention and Treatment of Viral Infections","volume":"55","author":"Moirangthem","year":"2025","journal-title":"Eur. J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/s41590-022-01130-4","article-title":"Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses","volume":"23","author":"Tomalka","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41586-024-07748-8","article-title":"Immunological memory diversity in the human upper airway","volume":"632","author":"Ramirez","year":"2024","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"eabl9105","DOI":"10.1126\/sciimmunol.abl9105","article-title":"SARS-CoV-2 infection generates tissue-localized immunological memory in humans","volume":"6","author":"Poon","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/imr.13112","article-title":"Tissue immunity to SARS-CoV-2: Role in protection and immunopathology","volume":"309","author":"Rybkina","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"9215","DOI":"10.3390\/cimb45110577","article-title":"Head and Neck Squamous Cell Carcinoma Vaccine: Current Landscape and Perspectives","volume":"45","author":"Meliante","year":"2023","journal-title":"Curr. Issues Mol. Biol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/6\/848\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:51:48Z","timestamp":1760032308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/6\/848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,13]]},"references-count":91,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["v17060848"],"URL":"https:\/\/doi.org\/10.3390\/v17060848","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,13]]}}}