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Mouse models that induce mammary tumorigenesis through Cre-mediated genetic manipulations can be used to study these early events. However, the immune effects of different induction methods remain unclear. Here, we compare adenovirus-delivered Cre with tamoxifen-inducible CreER systems in models targeting luminal mammary epithelial cells for p53-loss. We find that transient intraductal adenoviral infection produces not only an acute immune response but also long-lasting reshaping of the mammary gland immune microenvironment. Adenovirus exposure induces robust and persistent CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell infiltration dominated by CD103\n                    <jats:sup>+<\/jats:sup>\n                    tissue-resident T cells displaying heightened activation. This sustained antiviral T-cell signature obscures the p53-loss-driven CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell activation detectable in the CreER\/tamoxifen model. Adenoviral infection also transiently skews CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells toward IFN-\u03b3-producing antiviral states and affects the myeloid compartment, whereas tamoxifen-induced p53-loss increases macrophage abundance and activates CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells during premalignancy. Despite similar tumor latencies across induction strategies, our findings demonstrate that adenoviral infection exerts long-term immunological effects that can confound interpretation of immune dynamics during early mammary tumorigenesis. These results emphasize the importance of induction-method selection when using genetically engineered mouse models to study cancer-immune interactions.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-43069-8","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T12:45:32Z","timestamp":1773319532000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transient adenovirus-Cre infection causes long-lasting remodeling of the mammary gland immune landscape"],"prefix":"10.1038","volume":"16","author":[{"given":"Sen","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chujun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-0885","authenticated-orcid":false,"given":"Zhe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"43069_CR1","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","volume":"140","author":"SI Grivennikov","year":"2010","unstructured":"Grivennikov, S. 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