{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:27:52Z","timestamp":1792517272914,"version":"4.5.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515010464"],"award-info":[{"award-number":["2023A1515010464"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Human papillomavirus (HPV) infection has become an important etiological driver of oropharyngeal squamous cell carcinoma (OPSCC), leading to unique tumor characteristics. However, the interplay between HPV-associated tumor cells and tumor microenvironment (TME) remains an enigma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed a single-cell RNA-sequencing (scRNA-seq) on HPV-positive (HPV<jats:sup>+<\/jats:sup>) and HPV-negative (HPV<jats:sup>\u2012<\/jats:sup>) OPSCC tumors, each for three samples, and one normal tonsil tissue. Ex vivo validation assays including immunofluorescence staining, cell line co-culture, and flow cytometry analysis were used to test specific subtypes of HPV<jats:sup>+<\/jats:sup> tumor cells and their communications with T cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Through a comprehensive single-cell transcriptome analysis, we uncover the distinct transcriptional signatures between HPV<jats:sup>+<\/jats:sup> and HPV<jats:sup>\u2012<\/jats:sup> OPSCC. Specifically, HPV<jats:sup>+<\/jats:sup> OPSCC tumor cells manifest an enhanced interferon response and elevated expression of the major histocompatibility complex II (MHC-II), potentially bolstering tumor recognition and immune response. Furthermore, we identify a CXCL13<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cell subset that exhibits dual features of both follicular and pro-inflammatory helper T cells. Noteworthily, HPV<jats:sup>+<\/jats:sup> OPSCC tumor cells embrace extensive intercellular communications with CXCL13<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells. Interaction with HPV<jats:sup>+<\/jats:sup> OPSCC tumor cells amplifies CXCL13 and IFN\u03b3 release in CD4<jats:sup>+<\/jats:sup>T cells, fostering a pro-inflammatory TME. Additionally, HPV<jats:sup>+<\/jats:sup> tumor cells expressing high MHC-II and CXCL13<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cell prevalence are indicative of favorable overall survival rates in OPSCC patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Together, our study underscores a synergistic inflammatory immune response orchestrated by highly immunogenic tumor cells and CXCL13<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells in HPV<jats:sup>+<\/jats:sup> OPSCC, offering useful insights into strategy development for patient stratification and effective immunotherapy in OPSCC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00262-024-03789-0","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T13:08:23Z","timestamp":1722949703000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Deciphering the interplay of HPV infection, MHC-II expression, and CXCL13+ CD4+ T cell activation in oropharyngeal cancer: implications for immunotherapy"],"prefix":"10.1007","volume":"73","author":[{"given":"Shida","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaohong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyuan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingtao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Bei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"issue":"1","key":"3789_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1056\/NEJMra1715715","volume":"382","author":"LQM Chow","year":"2020","unstructured":"Chow LQM (2020) Head and neck cancer. N Engl J Med 382(1):60\u201372. https:\/\/doi.org\/10.1056\/NEJMra1715715","journal-title":"N Engl J Med"},{"issue":"5","key":"3789_CR2","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/s41571-022-00603-7","volume":"19","author":"M Lechner","year":"2022","unstructured":"Lechner M, Liu J, Masterson L, Fenton TR (2022) HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management. Nat Rev Clin Oncol 19(5):306\u2013327. https:\/\/doi.org\/10.1038\/s41571-022-00603-7","journal-title":"Nat Rev Clin Oncol"},{"issue":"4","key":"3789_CR3","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1021\/tx500034c","volume":"27","author":"AP Stein","year":"2014","unstructured":"Stein AP, Saha S, Yu M, Kimple RJ, Lambert PF (2014) Prevalence of human papillomavirus in oropharyngeal squamous cell carcinoma in the United States across time. Chem Res Toxicol 27(4):462\u2013469. https:\/\/doi.org\/10.1021\/tx500034c","journal-title":"Chem Res Toxicol"},{"key":"3789_CR4","doi-asserted-by":"publisher","first-page":"619","DOI":"10.3389\/fonc.2018.00619","volume":"8","author":"L Guo","year":"2018","unstructured":"Guo L, Yang F, Yin Y et al (2018) Prevalence of human papillomavirus type-16 in head and neck cancer among the chinese population: a meta-analysis. Front Oncol 8:619. https:\/\/doi.org\/10.3389\/fonc.2018.00619","journal-title":"Front Oncol"},{"issue":"1","key":"3789_CR5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1056\/NEJMoa0912217","volume":"363","author":"KK Ang","year":"2010","unstructured":"Ang KK, Harris J, Wheeler R et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24\u201335. https:\/\/doi.org\/10.1056\/NEJMoa0912217","journal-title":"N Engl J Med"},{"issue":"8","key":"3789_CR6","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1158\/2159-8290.CD-20-1760","volume":"11","author":"AA Shamseddine","year":"2021","unstructured":"Shamseddine AA, Burman B, Lee NY, Zamarin D, Riaz N (2021) Tumor immunity and immunotherapy for HPV-related cancers. Cancer Discov 11(8):1896\u20131912. https:\/\/doi.org\/10.1158\/2159-8290.CD-20-1760","journal-title":"Cancer Discov"},{"key":"3789_CR7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.645170","volume":"12","author":"Y Xu","year":"2021","unstructured":"Xu Y, Zhu G, Maroun CA et al (2021) Programmed death-1\/programmed death-ligand 1-axis blockade in recurrent or metastatic head and neck squamous cell carcinoma stratified by human papillomavirus status: a systematic review and meta-analysis. Front Immunol 12:645170. https:\/\/doi.org\/10.3389\/fimmu.2021.645170","journal-title":"Front Immunol"},{"key":"3789_CR8","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.omtn.2020.08.030","volume":"22","author":"X Zhang","year":"2020","unstructured":"Zhang X, Shi M, Chen T, Zhang B (2020) Characterization of the immune cell infiltration landscape in head and neck squamous cell carcinoma to aid immunotherapy. Mol Ther Nucleic Acids 22:298\u2013309. https:\/\/doi.org\/10.1016\/j.omtn.2020.08.030","journal-title":"Mol Ther Nucleic Acids"},{"issue":"10167","key":"3789_CR9","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/s0140-6736(18)31999-8","volume":"393","author":"EEW Cohen","year":"2019","unstructured":"Cohen EEW, Souli\u00e8res D, Le Tourneau C et al (2019) Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 393(10167):156\u2013167. https:\/\/doi.org\/10.1016\/s0140-6736(18)31999-8","journal-title":"Lancet"},{"issue":"8","key":"3789_CR10","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/s1470-2045(17)30421-7","volume":"18","author":"KJ Harrington","year":"2017","unstructured":"Harrington KJ, Ferris RL, Blumenschein G et al (2017) Nivolumab versus standard, single-agent therapy of investigator\u2019s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol 18(8):1104\u20131115. https:\/\/doi.org\/10.1016\/s1470-2045(17)30421-7","journal-title":"Lancet Oncol"},{"issue":"2","key":"3789_CR11","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/bjc.2013.639","volume":"110","author":"MJ Ward","year":"2014","unstructured":"Ward MJ, Thirdborough SM, Mellows T et al (2014) Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer. Br J Cancer 110(2):489\u2013500. https:\/\/doi.org\/10.1038\/bjc.2013.639","journal-title":"Br J Cancer"},{"key":"3789_CR12","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2018.1535293","author":"A Lechner","year":"2019","unstructured":"Lechner A, Schl\u00f6\u00dfer HA, Thelen M et al (2019) Tumor-associated B cells and humoral immune response in head and neck squamous cell carcinoma. OncoImmunology. https:\/\/doi.org\/10.1080\/2162402x.2018.1535293","journal-title":"OncoImmunology"},{"issue":"1","key":"3789_CR13","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.immuni.2019.11.014","volume":"52","author":"AR Cillo","year":"2020","unstructured":"Cillo AR, Kurten CHL, Tabib T et al (2020) Immune landscape of viral- and carcinogen-driven head and neck cancer. Immunity 52(1):183\u2013199. https:\/\/doi.org\/10.1016\/j.immuni.2019.11.014","journal-title":"Immunity"},{"issue":"1","key":"3789_CR14","doi-asserted-by":"publisher","first-page":"7338","DOI":"10.1038\/s41467-021-27619-4","volume":"12","author":"CHL Kurten","year":"2021","unstructured":"Kurten CHL, Kulkarni A, Cillo AR et al (2021) Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing. Nat Commun 12(1):7338. https:\/\/doi.org\/10.1038\/s41467-021-27619-4","journal-title":"Nat Commun"},{"issue":"10","key":"3789_CR15","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1158\/1078-0432.CCR-21-3570","volume":"28","author":"A Obradovic","year":"2022","unstructured":"Obradovic A, Graves DA-O, Korrer MA-O et al (2022) Immunostimulatory cancer-associated fibroblast subpopulations can predict immunotherapy response in head and neck cancer. Clin Cancer Res 28(10):2094\u20132109","journal-title":"Clin Cancer Res"},{"key":"3789_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2931-3","author":"A Wieland","year":"2020","unstructured":"Wieland A, Patel MR, Cardenas MA et al (2020) Defining HPV-specific B cell responses in patients with head and neck cancer. Nature. https:\/\/doi.org\/10.1038\/s41586-020-2931-3","journal-title":"Nature"},{"key":"3789_CR17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200389","author":"KH Bhatt","year":"2020","unstructured":"Bhatt KH, Neller MA, Srihari S et al (2020) Profiling HPV-16-specific T cell responses reveals broad antigen reactivities in oropharyngeal cancer patients. J Exp Med. https:\/\/doi.org\/10.1084\/jem.20200389","journal-title":"J Exp Med"},{"issue":"2","key":"3789_CR18","doi-asserted-by":"publisher","first-page":"122","DOI":"10.3322\/caac.21389","volume":"67","author":"WM Lydiatt","year":"2017","unstructured":"Lydiatt WM, Patel SG, O\u2019Sullivan B et al (2017) Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin 67(2):122\u2013137. https:\/\/doi.org\/10.3322\/caac.21389","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"3789_CR19","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/s13059-020-02210-0","volume":"21","author":"S He","year":"2020","unstructured":"He S, Wang LH, Liu Y et al (2020) Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs. Genome Biol 21(1):294. https:\/\/doi.org\/10.1186\/s13059-020-02210-0","journal-title":"Genome Biol"},{"key":"3789_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303913","author":"YQ Li","year":"2023","unstructured":"Li YQ, Luo CL, Jiang JX et al (2023) Single-cell analysis reveals malignant cells reshape the cellular landscape and foster an immunosuppressive microenvironment of extranodal NK\/T-cell lymphoma. Adv Sci (Weinh). https:\/\/doi.org\/10.1002\/advs.202303913","journal-title":"Adv Sci (Weinh)."},{"issue":"7","key":"3789_CR21","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart T, Butler A, Hoffman P et al (2019) Comprehensive integration of single-cell data. Cell 177(7):1888\u20131902. https:\/\/doi.org\/10.1016\/j.cell.2019.05.031","journal-title":"Cell"},{"issue":"4","key":"3789_CR22","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","volume":"8","author":"CS McGinnis","year":"2019","unstructured":"McGinnis CS, Murrow LM, Gartner ZJ (2019) DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst 8(4):329\u2013337. https:\/\/doi.org\/10.1016\/j.cels.2019.03.003","journal-title":"Cell Syst"},{"issue":"6190","key":"3789_CR23","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1126\/science.1254257","volume":"344","author":"AP Patel","year":"2014","unstructured":"Patel AP, Tirosh I, Trombetta JJ et al (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344(6190):1396. https:\/\/doi.org\/10.1126\/science.1254257","journal-title":"Science"},{"issue":"8","key":"3789_CR24","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1038\/s41588-022-01141-9","volume":"54","author":"D Barkley","year":"2022","unstructured":"Barkley D, Moncada R, Pour M et al (2022) Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment. Nat Genet 54(8):1192\u20131201. https:\/\/doi.org\/10.1038\/s41588-022-01141-9","journal-title":"Nat Genet"},{"issue":"1","key":"3789_CR25","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2105-14-7","volume":"14","author":"S H\u00e4nzelmann","year":"2013","unstructured":"H\u00e4nzelmann S, Castelo R, Guinney J (2013) GSVA: gene set variation analysis for microarray and RNA-Seq data. BMC Bioinform 14(1):7. https:\/\/doi.org\/10.1186\/1471-2105-14-7","journal-title":"BMC Bioinform"},{"issue":"7745","key":"3789_CR26","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","volume":"566","author":"J Cao","year":"2019","unstructured":"Cao J, Spielmann M, Qiu X et al (2019) The single-cell transcriptional landscape of mammalian organogenesis. Nature 566(7745):496\u2013502. https:\/\/doi.org\/10.1038\/s41586-019-0969-x","journal-title":"Nature"},{"issue":"11","key":"3789_CR27","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","volume":"14","author":"S Aibar","year":"2017","unstructured":"Aibar S, Gonzalez-Blas CB, Moerman T et al (2017) SCENIC: single-cell regulatory network inference and clustering. Nat Methods 14(11):1083\u20131086. https:\/\/doi.org\/10.1038\/nmeth.4463","journal-title":"Nat Methods"},{"issue":"4","key":"3789_CR28","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1038\/s41596-020-0292-x","volume":"15","author":"M Efremova","year":"2020","unstructured":"Efremova M, Vento-Tormo M, Teichmann SA, Vento-Tormo R (2020) Cell PhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat Protoc 15(4):1484\u20131506. https:\/\/doi.org\/10.1038\/s41596-020-0292-x","journal-title":"Nat Protoc"},{"issue":"1","key":"3789_CR29","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.celrep.2018.03.063","volume":"23","author":"JD Campbell","year":"2018","unstructured":"Campbell JD, Yau C, Bowlby R et al (2018) Genomic, pathway network, and immunologic features distinguishing squamous carcinomas. Cell Rep 23(1):194\u2013212. https:\/\/doi.org\/10.1016\/j.celrep.2018.03.063","journal-title":"Cell Rep"},{"issue":"1","key":"3789_CR30","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s13059-021-02290-6","volume":"22","author":"H Jin","year":"2021","unstructured":"Jin H, Liu Z (2021) A benchmark for RNA-seq deconvolution analysis under dynamic testing environments. Genome Biol 22(1):102. https:\/\/doi.org\/10.1186\/s13059-021-02290-6","journal-title":"Genome Biol"},{"issue":"1","key":"3789_CR31","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/s41467-018-08023-x","volume":"10","author":"X Wang","year":"2019","unstructured":"Wang X, Park J, Susztak K, Zhang NR, Li M (2019) Bulk tissue cell type deconvolution with multi-subject single-cell expression reference. Nat Commun 10(1):380. https:\/\/doi.org\/10.1038\/s41467-018-08023-x","journal-title":"Nat Commun"},{"issue":"7","key":"3789_CR32","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","volume":"37","author":"AM Newman","year":"2019","unstructured":"Newman AM, Steen CB, Liu CL et al (2019) Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat Biotechnol 37(7):773\u2013782. https:\/\/doi.org\/10.1038\/s41587-019-0114-2","journal-title":"Nat Biotechnol"},{"issue":"10","key":"3789_CR33","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1498439","volume":"7","author":"SF Gameiro","year":"2018","unstructured":"Gameiro SF, Ghasemi F, Barrett JW et al (2018) Treatment-naive HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV-counterparts that has implications for immunotherapy. Oncoimmunology 7(10):e1498439. https:\/\/doi.org\/10.1080\/2162402X.2018.1498439","journal-title":"Oncoimmunology"},{"issue":"7536","key":"3789_CR34","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/nature14129","volume":"517","author":"N Cancer Genome Atlas","year":"2015","unstructured":"Cancer Genome Atlas N (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517(7536):576\u201382. https:\/\/doi.org\/10.1038\/nature14129","journal-title":"Nature"},{"key":"3789_CR35","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13061230","author":"Z Qi","year":"2021","unstructured":"Qi Z, Liu Y, Mints M et al (2021) Single-cell deconvolution of head and neck squamous cell carcinoma. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers13061230","journal-title":"Cancers (Basel)."},{"key":"3789_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/v9080206","author":"TR Litwin","year":"2017","unstructured":"Litwin TR, Clarke MA, Dean M, Wentzensen N (2017) Somatic host cell alterations in HPV carcinogenesis. Viruses. https:\/\/doi.org\/10.3390\/v9080206","journal-title":"Viruses"},{"issue":"Suppl 5","key":"3789_CR37","doi-asserted-by":"publisher","first-page":"F55","DOI":"10.1016\/j.vaccine.2012.06.083","volume":"30","author":"J Doorbar","year":"2012","unstructured":"Doorbar J, Quint W, Banks L et al (2012) The biology and life-cycle of human papillomaviruses. Vaccine 30(Suppl 5):F55-70. https:\/\/doi.org\/10.1016\/j.vaccine.2012.06.083","journal-title":"Vaccine"},{"issue":"8","key":"3789_CR38","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1158\/1078-0432.CCR-18-3200","volume":"25","author":"ML Axelrod","year":"2019","unstructured":"Axelrod ML, Cook RS, Johnson DB, Balko JM (2019) Biological consequences of MHC-II expression by tumor cells in cancer. Clin Cancer Res 25(8):2392\u20132402. https:\/\/doi.org\/10.1158\/1078-0432.CCR-18-3200","journal-title":"Clin Cancer Res"},{"key":"3789_CR39","doi-asserted-by":"publisher","first-page":"10582","DOI":"10.1038\/ncomms10582","volume":"7","author":"DB Johnson","year":"2016","unstructured":"Johnson DB, Estrada MV, Salgado R et al (2016) Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1\/PD-L1 therapy. Nat Commun 7:10582. https:\/\/doi.org\/10.1038\/ncomms10582","journal-title":"Nat Commun"},{"issue":"7","key":"3789_CR40","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1038\/s41590-020-0706-5","volume":"21","author":"J Choi","year":"2020","unstructured":"Choi J, Diao H, Faliti CE et al (2020) Bcl-6 is the nexus transcription factor of T follicular helper cells via repressor-of-repressor circuits. Nat Immunol 21(7):777\u2013789. https:\/\/doi.org\/10.1038\/s41590-020-0706-5","journal-title":"Nat Immunol"},{"issue":"3","key":"3789_CR41","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.781","volume":"12","author":"H Wu","year":"2022","unstructured":"Wu H, Deng Y, Long D et al (2022) The IL-21-TET2-AIM2-c-MAF pathway drives the T follicular helper cell response in lupus-like disease. Clin Transl Med 12(3):e781. https:\/\/doi.org\/10.1002\/ctm2.781","journal-title":"Clin Transl Med"},{"issue":"3","key":"3789_CR42","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s00011-016-0995-1","volume":"66","author":"H Su","year":"2017","unstructured":"Su H, Na N, Zhang X, Zhao Y (2017) The biological function and significance of CD74 in immune diseases. Inflamm Res 66(3):209\u2013216. https:\/\/doi.org\/10.1007\/s00011-016-0995-1","journal-title":"Inflamm Res"},{"issue":"74","key":"3789_CR43","doi-asserted-by":"publisher","first-page":"eabn6373","DOI":"10.1126\/sciimmunol.abn6373","volume":"7","author":"B Li","year":"2022","unstructured":"Li B, Lu Y, Zhong M-C et al (2022) Cis interactions between CD2 and its ligands on T cells are required for T cell activation. Sci Immunol 7(74):eabn6373. https:\/\/doi.org\/10.1126\/sciimmunol.abn6373","journal-title":"Sci Immunol"},{"issue":"5","key":"3789_CR44","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1016\/j.immuni.2019.04.011","volume":"50","author":"S Crotty","year":"2019","unstructured":"Crotty S (2019) T follicular helper cell biology: a decade of discovery and diseases. Immunity 50(5):1132\u20131148. https:\/\/doi.org\/10.1016\/j.immuni.2019.04.011","journal-title":"Immunity"},{"key":"3789_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11081129","author":"SF Gameiro","year":"2019","unstructured":"Gameiro SF, Ghasemi F, Barrett JW, Nichols AC, Mymryk JS (2019) High level expression of MHC-II in HPV+ head and neck cancers suggests that tumor epithelial cells serve an important role as accessory antigen presenting cells. Cancers. https:\/\/doi.org\/10.3390\/cancers11081129","journal-title":"Cancers"},{"issue":"3","key":"3789_CR46","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/s41416-021-01400-2","volume":"125","author":"E Schaafsma","year":"2021","unstructured":"Schaafsma E, Fugle CM, Wang X, Cheng C (2021) Pan-cancer association of HLA gene expression with cancer prognosis and immunotherapy efficacy. Br J Cancer 125(3):422\u2013432. https:\/\/doi.org\/10.1038\/s41416-021-01400-2","journal-title":"Br J Cancer"},{"issue":"450","key":"3789_CR47","doi-asserted-by":"publisher","first-page":"eaar3342","DOI":"10.1126\/scitranslmed.aar3342","volume":"10","author":"J Rodig Scott","year":"2018","unstructured":"Rodig Scott J, Gusenleitner D, Jackson Donald G et al (2018) MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma. Sci Trans Med 10(450):eaar3342. https:\/\/doi.org\/10.1126\/scitranslmed.aar3342","journal-title":"Sci Trans Med"},{"issue":"10","key":"3789_CR48","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1200\/JCO.2017.77.3994","volume":"36","author":"MGM Roemer","year":"2018","unstructured":"Roemer MGM, Redd RA, Cader FZ et al (2018) Major histocompatibility complex class II and programmed death ligand 1 expression predict outcome after programmed death 1 blockade in classic hodgkin lymphoma. J Clin Oncol 36(10):942\u2013950. https:\/\/doi.org\/10.1200\/JCO.2017.77.3994","journal-title":"J Clin Oncol"},{"issue":"8","key":"3789_CR49","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1172\/JCI91190","volume":"127","author":"M Ayers","year":"2017","unstructured":"Ayers M, Lunceford J, Nebozhyn M et al (2017) IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest 127(8):2930\u20132940. https:\/\/doi.org\/10.1172\/JCI91190","journal-title":"J Clin Invest"},{"issue":"10","key":"3789_CR50","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/s41577-018-0044-0","volume":"18","author":"J Borst","year":"2018","unstructured":"Borst J, Ahrends T, Babala N, Melief CJM, Kastenmuller W (2018) CD4(+) T cell help in cancer immunology and immunotherapy. Nat Rev Immunol 18(10):635\u2013647. https:\/\/doi.org\/10.1038\/s41577-018-0044-0","journal-title":"Nat Rev Immunol"},{"issue":"6574","key":"3789_CR51","doi-asserted-by":"publisher","first-page":"abe6474","DOI":"10.1126\/science.abe6474","volume":"374","author":"L Zheng","year":"2021","unstructured":"Zheng L, Qin S, Si W et al (2021) Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science 374(6574):abe6474. https:\/\/doi.org\/10.1126\/science.abe6474","journal-title":"Science"},{"issue":"6","key":"3789_CR52","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1038\/s41591-023-02345-0","volume":"29","author":"A Magen","year":"2023","unstructured":"Magen A, Hamon P, Fiaschi N et al (2023) Intratumoral dendritic cell\u2013CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma. Nat Med 29(6):1389\u20131399. https:\/\/doi.org\/10.1038\/s41591-023-02345-0","journal-title":"Nat Med"},{"issue":"13","key":"3789_CR53","doi-asserted-by":"publisher","first-page":"6886","DOI":"10.1073\/pnas.94.13.6886","volume":"94","author":"TD Armstrong","year":"1997","unstructured":"Armstrong TD, Clements VK, Martin BK, Ting JPY, Ostrand-Rosenberg S (1997) Major histocompatibility complex class II-transfected tumor cells present endogenous antigen and are potent inducers of\u2009tumor-specific\u2009immunity. Proc Natl Acad Sci 94(13):6886\u20136891. https:\/\/doi.org\/10.1073\/pnas.94.13.6886","journal-title":"Proc Natl Acad Sci"},{"issue":"6","key":"3789_CR54","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1016\/j.cell.2016.11.022","volume":"167","author":"JL Benci","year":"2016","unstructured":"Benci JL, Bihui X, Qiu Y et al (2016) Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell 167(6):1540-1554.e12. https:\/\/doi.org\/10.1016\/j.cell.2016.11.022","journal-title":"Cell"},{"issue":"4","key":"3789_CR55","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.immuni.2022.03.007","volume":"55","author":"L Cucolo","year":"2022","unstructured":"Cucolo L, Chen Q, Qiu J et al (2022) The interferon-stimulated gene RIPK1 regulates cancer cell intrinsic and extrinsic resistance to immune checkpoint blockade. Immunity 55(4):671\u2013685. https:\/\/doi.org\/10.1016\/j.immuni.2022.03.007","journal-title":"Immunity"},{"key":"3789_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104373","author":"PYF Zeng","year":"2022","unstructured":"Zeng PYF, Cecchini MJ, Barrett JW et al (2022) Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification. eBioMedicine. https:\/\/doi.org\/10.1016\/j.ebiom.2022.104373","journal-title":"eBioMedicine"},{"issue":"10","key":"3789_CR57","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1093\/annonc\/mdz271","volume":"30","author":"B Solomon","year":"2019","unstructured":"Solomon B, Young RJ, Bressel M et al (2019) Identification of an excellent prognosis subset of human papillomavirus-associated oropharyngeal cancer patients by quantification of intratumoral CD103+ immune cell abundance. Ann Oncol 30(10):1638\u20131646. https:\/\/doi.org\/10.1093\/annonc\/mdz271","journal-title":"Ann Oncol"},{"issue":"7","key":"3789_CR58","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1016\/j.cell.2017.10.044","volume":"171","author":"SV Puram","year":"2017","unstructured":"Puram SV, Tirosh I, Parikh AS et al (2017) Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell 171(7):1611\u20131624. https:\/\/doi.org\/10.1016\/j.cell.2017.10.044","journal-title":"Cell"},{"issue":"9","key":"3789_CR59","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1038\/s43018-022-00433-7","volume":"3","author":"B Liu","year":"2022","unstructured":"Liu B, Zhang Y, Wang D, Hu X, Zhang Z (2022) Single-cell meta-analyses reveal responses of tumor-reactive CXCL13(+) T cells to immune-checkpoint blockade. Nat Cancer 3(9):1123\u20131136","journal-title":"Nat Cancer"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-024-03789-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-024-03789-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-024-03789-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T18:08:04Z","timestamp":1726510084000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-024-03789-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":59,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["3789"],"URL":"https:\/\/doi.org\/10.1007\/s00262-024-03789-0","relation":{},"ISSN":["1432-0851"],"issn-type":[{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]},"assertion":[{"value":"30 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Ethical approval was obtained from the Institutional Review Board of Sun Yat-sen University Cancer Center and written informed consent was obtained from all participants before specimen collection.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"206"}}