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Whether KRAS inhibition leads to CCA tumor regression is unknown, partly due to the lack of conditional animal models. A conditional TRE.\n                    <jats:italic>Kras<\/jats:italic>\n                    <jats:sup>G12D<\/jats:sup>\n                    \/\n                    <jats:italic>Trp53<\/jats:italic>\n                    knock\u2010out (TKP) CCA mouse model is engineered using the transposon system and CRISPR\u2010Cas9. Withdrawal of\n                    <jats:italic>Kras<\/jats:italic>\n                    <jats:sup>G12D<\/jats:sup>\n                    results in &gt;90% tumor regression by day 7, accompanied by infiltration and enrichment of activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, shown by IHC, co\u2010IF staining, and single\u2010cell RNA\u2010Seq. Bulk RNA\u2010Seq of TKP cell line suggested that\n                    <jats:italic>Kras<\/jats:italic>\n                    <jats:sup>G12D<\/jats:sup>\n                    withdrawal stimulates the transforming growth factor beta pathway and induces senescence. Cytokine array characterizes the secretion of pro\u2010inflammatory factors, including IL\u201015 and CCL17. Lentiviral overexpression of murine IL\u201015 and CCL17 delays CCA tumor progression in a syngeneic transplant model. Consistently, expression of IL\u201015 resulted in blockade of tumor progression in the TKP CCA model. These findings highlight the importance of oncogenic\n                    <jats:italic>Kras<\/jats:italic>\n                    in CCA tumor maintenance and underscore KRAS inhibition as a potential therapeutic approach for CCA.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511312","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T09:09:38Z","timestamp":1764752978000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["KRAS Withdrawal in Cholangiocarcinoma Leads to Immune Infiltration and Tumor Regression"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8495-2097","authenticated-orcid":false,"given":"Youwei","family":"Qiao","sequence":"first","affiliation":[{"name":"RNA Therapeutics Institute University of Massachusetts Chan Medical School Worcester MA 01605 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew 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