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Engineered T cells expressing MSLN\u2010reactive high\u2010affinity TCR exhibit extraordinary therapeutic effects for invasive pancreatic ductal adenocarcinoma in a mouse model. However, the generation of MSLN\u2010reactive T cells through the introduction of <jats:italic>MSLN<\/jats:italic>\u2010deficient thymus and the transplantation of the latter as a cure for cancer treatment have not been tested to date. In the present study, the expression of MSLN was mainly identified in medullary thymic epithelial cells (mTECs) but not in hematopoietic cells, cortical thymic epithelial cells (cTECs), endothelial cells, or fibroblast cells in the thymus. The increasement of activated T cells was observed in MSLN\u2010expressing tumors from <jats:italic>MSLN<\/jats:italic>\u2010deficient mice, indicating that MSLN\u2010reactive T cells had developed. Finally, in an AOM\u2010DSS\u2010induced mouse model of colorectal cancer (CRC), transplantation of <jats:italic>MSLN<\/jats:italic>\u2010deficient thymus repressed the progression of CRC, accompanied by an increased number of IFN\u03b3\u2010expressing T lymphocytes in the tumors. The data from this study demonstrated that ectopic transplantation of <jats:italic>MSLN<\/jats:italic>\u2010deficient thymus induced MSLN\u2010specific antitumor responses to MSLN\u2010expressing tumors, and thus attenuated tumor progression.<\/jats:p>","DOI":"10.1111\/cas.16458","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T01:14:49Z","timestamp":1737681289000},"page":"871-883","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transplantation of the <scp><i>MSLN<\/i><\/scp>\u2010deficient Thymus Generates <scp>MSLN<\/scp> Epitope Reactive T Cells to Attenuate Tumor Progression"],"prefix":"10.1111","volume":"116","author":[{"given":"Hanchao","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Nephrology, Shenzhen Longhua District Central Hospital Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease  Shenzhen 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