{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:46:02Z","timestamp":1793450762156,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022TSYCLJ0031"],"award-info":[{"award-number":["2022TSYCLJ0031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chemoresistance remains a major challenge in esophageal squamous cell carcinoma (ESCC) therapy, particularly resistance to 5\u2010Fluorouracil (5\u2010FU). This study uncovers how 5\u2010FU resistance reprograms the tumour microenvironment, primarily through the up\u2010regulation of ADAM10 and the release of soluble PD\u2010L1, which collectively facilitate immune evasion. Using a 5\u2010FU\u2010resistant AKR mouse ESCC cell line (5\u2010FU\u2010AKR) and its parental counterpart, we applied third\u2010generation DNA sequencing, proteomic analysis, and single\u2010cell RNA sequencing to unravel the resistance\u2010associated molecular and cellular shifts. We found that ADAM10 is significantly up\u2010regulated in 5\u2010FU\u2010AKR cells, promoting soluble PD\u2010L1 release, thereby limiting CD8+ T cell infiltration. Xenograft models further demonstrated enhanced tumourigenicity and immune exclusion in 5\u2010FU\u2010resistant tumours. These findings highlight a novel mechanism of immune suppression driven by ADAM10, suggesting that targeting the ADAM10\u2010PD\u2010L1 axis may restore anti\u2010tumour immunity and improve treatment outcomes for 5\u2010FU\u2010resistant ESCC.<\/jats:p>","DOI":"10.1111\/imm.70038","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T04:30:06Z","timestamp":1758083406000},"page":"170-184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["5\u2010\n                    <scp>FU<\/scp>\n                    Resistance Facilitates Immune Evasion in Esophageal Squamous Cell Carcinoma Through\n                    <scp>ADAM10<\/scp>\n                    \u2010Mediated\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    Shedding and Tumour Microenvironment 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