{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:18:23Z","timestamp":1784546303882,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are the most prevalent types of nonmelanoma skin cancer (NMSC) and exhibit significant inter\u2010 and intra\u2010tumor heterogeneity. cSCC has a higher metastatic potential than BCC, accompanied by a considerable mortality rate. However, the detailed mechanisms of tumor evolution in cSCC have not yet been described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed single\u2010cell RNA sequencing (scRNA\u2010seq) and T cell receptor (TCR) clonal analysis of skin biopsies from five BCCs, three squamous cell carcinomas in\u00a0situ (SCCIS), and two invasive squamous cell carcinomas (SCC). Independent SCC specimens were used for spatial transcriptomic (ST) analysis using GeoMx Digital Spatial Profiler (DSP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      Using scRNA\u2010seq, we analyzed a total of 117,663 cells. We distinguished cancer cells using copy number variation and identified SCC\u2010specific genes that potentially contribute to tumor progression. Analysis of tumor clones revealed SCC\u2010specific\n                      <jats:italic>COL6A1<\/jats:italic>\n                      +\/\n                      <jats:italic>ITGA5<\/jats:italic>\n                      + carcinoma cells which produce\n                      <jats:italic>CXCL16<\/jats:italic>\n                      . We also annotated\n                      <jats:italic>CXCR6<\/jats:italic>\n                      + regulatory T cells (Tregs) which potentially move toward the tumor site by CXCL16, shaping the immunosuppressive TME. ST analysis supported these clones were located at the invasion site of SCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We suggest COL6A1 and ITGA5 promote the invasive and metastatic property of SCC. We also uncovered how SCC recruits Tregs via the CXCL16\/CXCR6 axis to create a TME favorable for its survival. These molecules can be used as potential therapeutic targets for treatment of SCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71060","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T04:31:21Z","timestamp":1754627481000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>CXCL16<\/scp>\n                    Producing Tumor Clones Are Shaping Immunosuppressive Microenvironment in Squamous Cell Carcinoma via\n                    <scp>CXCR6<\/scp>\n                    Regulatory T Cell"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6217-4714","authenticated-orcid":false,"given":"Hyun Seung","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Seoul National University Graduate School  Seoul the Republic of Korea"},{"name":"Cancer Research Institute Seoul National University College of 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Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Seoul National University Boramae Hospital, Seoul National University College of Medicine  Seoul the Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanha","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Seoul National University Graduate School  Seoul the Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Min","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Seoul National University Graduate School  Seoul the Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade N.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Dermatology Icahn School of Medicine at Mount Sinai  New York 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