{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:06:29Z","timestamp":1789023989026,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Anatomical Record"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Esophageal squamous cell carcinoma (ESCC) is recognized as one of the most prevalent malignancies globally, with a notably high incidence in China. The disease often presents with subtle symptoms in its early stages, resulting in diagnoses at mid to late stages, which diminishes the possibility for radical surgical intervention. Additionally, the effectiveness, side effects, and resistance associated with radiotherapy and chemotherapy further constrain their use in treating ESCC. The advent of immune checkpoint inhibitors has expanded the array of immunotherapeutic strategies available for managing this condition. This study aims to delineate the occurrence and distribution of specific immune cell types throughout the progression of ESCC, utilizing a 4\u2010NQO\u2010induced murine model that most accurately reflects the initiation and progression of ESCC as observed in humans. This model encompasses various stages of ESCC development, including normal (NOR), inflammation (INF), hyperplasia (HYP), dysplasia (DYS), carcinoma in situ (CIS), and invasive cancer (ICA). Immunohistochemical analysis reveals an increase in the number of Ki67\n                    <jats:sup>+<\/jats:sup>\n                    cells correlating with the advancement of ESCC, indicating elevated tumor cell proliferation. Notably, CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells are prominently observed during the dysplastic stage, while CD20\n                    <jats:sup>+<\/jats:sup>\n                    B cells and CD68\n                    <jats:sup>+<\/jats:sup>\n                    macrophages are more prevalent during the hyperplastic stage. Furthermore, CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells are actively involved in tumor recognition and elimination within the esophageal epithelium, whereas CD20\n                    <jats:sup>+<\/jats:sup>\n                    B cells and CD68\n                    <jats:sup>+<\/jats:sup>\n                    macrophages are primarily localized in the submucosal layer. This study underscores the role of immune cells in the pathogenesis of ESCC and suggests the timely application of immune checkpoint inhibitors may enhance anti\u2010tumor immunity.\n                  <\/jats:p>","DOI":"10.1002\/ar.70330","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:23:10Z","timestamp":1789021390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of the occurrence and distribution of specific immune cells throughout the\n                    <scp>esophageal squamous cell carcinoma<\/scp>\n                    progression"],"prefix":"10.1002","author":[{"given":"Mengyu","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0213-3929","authenticated-orcid":false,"given":"Na","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"issue":"1","key":"e_1_2_7_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22010073","article-title":"The many faces of Cd4+ T cells: Immunological and structural characteristics","volume":"22","author":"Chatzileontiadou D. S. M.","year":"2020","journal-title":"International Journal of Molecular Sciences"},{"issue":"1","key":"e_1_2_7_3_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in immunoregulation and therapeutics","volume":"8","author":"Chen S.","year":"2023","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-074962","article-title":"Advances in diagnosis and management of cancer of the esophagus","volume":"385","author":"Deboever N.","year":"2024","journal-title":"BMJ"},{"issue":"5","key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1056\/NEJMoa2111380","article-title":"Nivolumab combination therapy in advanced esophageal squamous\u2010cell carcinoma","volume":"386","author":"Doki Y.","year":"2022","journal-title":"New England Journal of Medicine"},{"issue":"6","key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/s41590-023-01517-x","article-title":"Cd4+ T cell calibration of antigen\u2010presenting cells optimizes antiviral Cd8+ T cell immunity","volume":"24","author":"Gressier E.","year":"2023","journal-title":"Nature Immunology"},{"issue":"1","key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jncc.2024.01.006","article-title":"Cancer incidence and mortality in China, 2022","volume":"4","author":"Han B.","year":"2022","journal-title":"Journal of the National Cancer Center"},{"issue":"1","key":"e_1_2_7_8_1","doi-asserted-by":"crossref","DOI":"10.1038\/s44276-025-00146-1","article-title":"B cells and tertiary lymphoid structures in cancer therapy response","volume":"3","author":"Hegoburu A.","year":"2025","journal-title":"BJC Reports"},{"issue":"5","key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/jjco\/hyz034","article-title":"Systemic treatment of advanced esophageal squamous cell carcinoma: Chemotherapy, molecular\u2010targeting therapy and immunotherapy","volume":"49","author":"Hirano H.","year":"2019","journal-title":"Japanese Journal of Clinical Oncology"},{"issue":"1","key":"e_1_2_7_10_1","doi-asserted-by":"crossref","DOI":"10.1186\/s40880-019-0427-z","article-title":"The immune landscape of esophageal cancer","volume":"39","author":"Huang T.\u2010X.","year":"2019","journal-title":"Cancer Communications"},{"issue":"7","key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.it.2016.04.010","article-title":"Targeted therapy and checkpoint immunotherapy combinations for the treatment of cancer","volume":"37","author":"Hughes P. 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M.","year":"2022","journal-title":"Molecular Medicine Reports"},{"issue":"11","key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1038\/s12276-023-01105-x","article-title":"Cd8 T\u2010cell subsets: Heterogeneity, functions, and therapeutic potential","volume":"55","author":"Koh C.\u2010H.","year":"2023","journal-title":"Experimental & Molecular Medicine"},{"issue":"22","key":"e_1_2_7_17_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232214304","article-title":"Esophageal squamous cancer from 4NQO\u2010induced mice model: CNV alterations","volume":"23","author":"Liu Z.","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"issue":"4","key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1200\/JCO.23.00975","article-title":"Perioperative atezolizumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable esophagogastric cancer: Interim results from the randomized, multicenter, phase II\/III DANTE\/IKF\u2010S633 trial","volume":"42","author":"Lorenzen S.","year":"2024","journal-title":"Journal of Clinical Oncology"},{"issue":"2","key":"e_1_2_7_19_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41416-020-01048-4","article-title":"Cytotoxic Cd8+ T cells in cancer and cancer immunotherapy","volume":"124","author":"Raskov H.","year":"2021","journal-title":"British Journal of Cancer"},{"issue":"4","key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.ccell.2020.03.017","article-title":"Acquired resistance to immune checkpoint inhibitors","volume":"37","author":"Schoenfeld A. 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E.","year":"2023","journal-title":"Nature Cancer"},{"issue":"1","key":"e_1_2_7_23_1","first-page":"37","article-title":"Esophageal cancer: Insights from mouse models","volume":"8","author":"T\u00e9treault M.\u2010P.","year":"2015","journal-title":"Cancer Growth and Metastasis"},{"issue":"2","key":"e_1_2_7_24_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.14740\/wjon1254","article-title":"Esophageal cancer: An updated surveillance epidemiology and end results database analysis","volume":"11","author":"Then E. O.","year":"2020","journal-title":"World Journal of Oncology"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.molimm.2019.01.014","article-title":"Fas\/Fasl signaling is critical for the survival of exhausted antigen\u2010specific Cd8+ T cells during tumor immune response","volume":"107","author":"Yajima T.","year":"2019","journal-title":"Molecular Immunology"},{"issue":"1","key":"e_1_2_7_26_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003497","article-title":"Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma","volume":"10","author":"Yang W.","year":"2022","journal-title":"Journal for Immunotherapy of Cancer"},{"issue":"1","key":"e_1_2_7_27_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-17492-y","article-title":"Single\u2010cell transcriptomic analysis in a mouse model deciphers cell transition states in the multistep development of esophageal cancer","volume":"11","author":"Yao J.","year":"2020","journal-title":"Nature Communications"},{"issue":"3","key":"e_1_2_7_28_1","doi-asserted-by":"crossref","DOI":"10.3892\/etm.2024.12403","article-title":"Expression of macrophage activation\u2010specific factors in hyperplastic scar tissue during hyperplasia phase by antibody array blotting membrane assay and its clinical significance","volume":"27","author":"Zhang Y.","year":"2024","journal-title":"Experimental and Therapeutic Medicine"},{"issue":"1","key":"e_1_2_7_29_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells12010114","article-title":"Research progress on the predicting factors and coping strategies for postoperative recurrence of esophageal cancer","volume":"12","author":"Zhang Y.","year":"2022","journal-title":"Cells"},{"issue":"9","key":"e_1_2_7_30_1","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1002\/ijc.34301","article-title":"Esophageal cancer in China: Practice and research in the new era","volume":"152","author":"Zhu H.","year":"2023","journal-title":"International Journal of Cancer"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1387975","article-title":"Regulation of Treg cells by cytokine signaling and co\u2010stimulatory molecules","volume":"15","author":"Zong Y.","year":"2024","journal-title":"Frontiers in Immunology"},{"issue":"7","key":"e_1_2_7_32_1","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1111\/j.1349-7006.2012.02288.x","article-title":"Estrogen receptor \u0391 and \u0392 in esophageal squamous cell carcinoma","volume":"103","author":"Zuguchi M.","year":"2012","journal-title":"Cancer Science"}],"container-title":["The Anatomical Record"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.70330","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ar.70330","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.70330","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:23:14Z","timestamp":1789021394000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/ar.70330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":31,"alternative-id":["10.1002\/ar.70330"],"URL":"https:\/\/doi.org\/10.1002\/ar.70330","archive":["Portico"],"relation":{},"ISSN":["1932-8486","1932-8494"],"issn-type":[{"value":"1932-8486","type":"print"},{"value":"1932-8494","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"assertion":[{"value":"2025-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ar.70330"}}