{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:48:25Z","timestamp":1785775705436,"version":"3.56.0"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"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":["82503561"],"award-info":[{"award-number":["82503561"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023QH108"],"award-info":[{"award-number":["ZR2023QH108"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M772104"],"award-info":[{"award-number":["2025M772104"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Yippee\u2010like 3 (YPEL3) has been implicated in the regulation of apoptosis, proliferation, and invasion in various cancers, but its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. Here, we integrated pan\u2010cancer data, TCGA\/GEO transcriptomes, DNA methylation profiles, and single\u2010cell RNA sequencing to explore YPEL3's expression, prognosis, and immune relevance in HNSCC. YPEL3 was downregulated in tumor tissues and correlated with better overall survival, particularly in advanced\u2010stage patients. Functional assays confirmed that YPEL3 suppressed proliferation, migration, and invasion while promoting apoptosis in\u00a0vitro; its knockdown accelerated tumor growth in\u00a0vivo. Bulk transcriptomics and TIMER analysis revealed that high YPEL3 expression was associated with increased stromal and immune infiltration, including CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Single\u2010cell analysis identified an epithelial subcluster (Epi.C3) enriched for YPEL3, expanded in tumors, and linked to poor prognosis. Mechanistically, YPEL3\u2010high epithelial cells secreted CXCL16, interacting with CXCR6 on CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells to promote immune engagement. YPEL3 regulated CXCL16 via CREB1 but not TFAP2C. Co\u2010culture assays showed that epithelial YPEL3 modulated the CXCL16\u2013CXCR6 axis in T cells. In\u00a0vivo, YPEL3 loss was associated with reduced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell infiltration and impaired CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell effector function, as indicated by decreased Granzyme B, Perforin, IFN\u2010\u03b3, and TNF\u2010\u03b1. Together, these findings identify YPEL3 as a tumor suppressor and an important mediator of epithelial\u2013immune crosstalk in HNSCC, linking epithelial differentiation\u2010associated states to antitumor immunity through the CREB1\/CXCL16\/CXCR6 axis.\n                  <\/jats:p>","DOI":"10.1111\/cas.70409","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T05:30:31Z","timestamp":1779773431000},"page":"2132-2151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epithelial YPEL3 Modulates CD8\n                    <sup>+<\/sup>\n                    T\u2010Cell Infiltration and Tumor Progression Through CREB1\u2013CXCL16 Signaling in HNSCC"],"prefix":"10.1111","volume":"117","author":[{"given":"Yalun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital Qingdao University  Yantai China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai China"},{"name":"School of Basic Medicine Qingdao University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital Qingdao University  Yantai China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital Qingdao University  Yantai China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congxian","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital Qingdao University  Yantai China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2541-806X","authenticated-orcid":false,"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Yantai Yuhuangding Hospital Qingdao University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianshu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Yantai Yuhuangding Hospital Qingdao University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Qingdao University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9789-1318","authenticated-orcid":false,"given":"Xicheng","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital Qingdao University  Yantai China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation  Yantai China"},{"name":"Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases  Yantai China"},{"name":"Yantai Key Laboratory of Otorhinolaryngologic Diseases  Yantai 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