{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:52:13Z","timestamp":1790628733713,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573442"],"award-info":[{"award-number":["82573442"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403773"],"award-info":[{"award-number":["82403773"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025T180600"],"award-info":[{"award-number":["2025T180600"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M760140"],"award-info":[{"award-number":["2024M760140"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tumor spatial architecture significantly influences immune responses, but the impact of regional variations on T cell exhaustion and clonality in human papillomavirus (HPV)\u2010related cervical squamous cell carcinoma (CESC) remains poorly understood. Using single\u2010cell RNA sequencing (scRNA\u2010seq,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200913) and TCR sequencing (scTCR\u2010seq,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20099), this study profiled T cells from paired tumor core and edge samples of patients with CESC. This was supplemented by bulk RNA\u2010seq data (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200941), TCGA datasets from three cancer types (CESC, head and neck squamous cell carcinoma, and lung squamous cell carcinoma), and scRNA\u2010seq data from colorectal cancer for broader validation. We found that CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, natural killer T (NKT) cells, and \u03b3\u03b4 T cells in the tumor core exhibited higher inhibitory and cytotoxicity scores, while CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells showed increased regulatory T (Treg) and cytotoxic features in the tumor core. Bulk RNA\u2010seq data confirmed elevated inhibitory and cytotoxic scores in the tumor core relative to the edge. Additionally, four subsets of exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells (CD8\n                    <jats:sup>+<\/jats:sup>\n                    Tex) were identified, including a stress\u2010associated subset characterized by heat shock protein (HSP) family gene expression, which was validated by immunofluorescence and inversely correlated with survival in patients with CESC undergoing radiotherapy. TCR analysis revealed clonal expansion and reduced clonal diversity in the tumor core. Notably, CD8\n                    <jats:sup>+<\/jats:sup>\n                    Teff\u2010CD160 cells displayed substantial clonal sharing across regions and were associated with a favorable prognosis. Overall, our findings highlight distinct T cell states between the tumor core and edge in HPV\u2010related CESC, offering insights into prognostic biomarkers and potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70912","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T10:06:23Z","timestamp":1775901983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tumor Core\u2010Edge Divergence in T\u2010Cell Exhaustion and Clonal Expansion in HPV\u2010Related Cervical Squamous Cell Carcinoma Unveiled by Simultaneous Single\u2010Cell RNA and TCR Sequencing"],"prefix":"10.1002","volume":"98","author":[{"given":"Tianyu","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Oncology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuomin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfu","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Oncology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Oncology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Affiliated Cancer Hospital of Gannan Medical University, Ganzhou Institute and Hospital  Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangbin","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Gynecology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0764-3792","authenticated-orcid":false,"given":"Qinyong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Oncology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32470-X"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13174"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.101157"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70043"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2025.103290"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-2833"},{"key":"e_1_2_12_9_1","first-page":"615","article-title":"Prognostic Factors for Post\u2010Recurrence Survival Among Patients With Locally Advanced Cervical Cancer Who Underwent Definitive Concurrent Chemoradiation","volume":"27","author":"Thongkhao P.","year":"2022","journal-title":"Reports of Practical Oncology and Radiotherapy"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add8977"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01264-9"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202204951"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.638374"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0096-5"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-024-00637-3"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28084"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859"},{"key":"e_1_2_12_19_1","first-page":"100141","volume-title":"Innovation","author":"Wu T.","year":"2021"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0045-3"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0355-0"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.06.043"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa611"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-024-03935-8"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.12.001"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0694-x"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022110757"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104612"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1219"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300348"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85834"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00834-9"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42634-3"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-0734"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15776"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01448-7"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-023-00690-0"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59535"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13436"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2010.10.014"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2013.108"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02371-y"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.03.007"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.70912","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmv.70912","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.70912","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:47:55Z","timestamp":1779367675000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.70912"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/jmv.70912"],"URL":"https:\/\/doi.org\/10.1002\/jmv.70912","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-11-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70912"}}