{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:04:47Z","timestamp":1783919087229,"version":"3.55.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Forschung, Technologie und Raumfahrt","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n \n Familial adenomatous polyposis (FAP) is a hereditary condition that almost invariably leads to colorectal cancer. While\n TP53<\/jats:italic>\n inactivation is well established as a late event in the adenoma-to-carcinoma sequence, its functional role during the early stage of colorectal polyp development remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Three lines of FAP pigs were generated:\n \n APC\n 1311\/+<\/jats:sup>\n <\/jats:italic>\n ,\n \n APC\n 1311\/+<\/jats:sup>\n <\/jats:italic>\n \/\n \n TP53\n +\/-<\/jats:sup>\n <\/jats:italic>\n , and\n \n APC\n 1311\/+<\/jats:sup>\n <\/jats:italic>\n \/\n \n TP53\n -\/-<\/jats:sup>\n <\/jats:italic>\n . Colonic polyp development was evaluated by colonoscopy at 3 and 9 months of age. Mucosal goblet cell and mucin content were assessed using periodic acid-Schiff\/Alcian blue (PAS-AB) staining. Immunohistochemistry for Ki67 and IBA1 was performed to assess epithelial proliferation and macrophage\/monocyte-like cell infiltration, respectively. Quantitative PCR was used to measure mRNA expression of macrophage\/monocyte - and complement-related genes, including\n CCL2<\/jats:italic>\n ,\n FCGR3A<\/jats:italic>\n ,\n ITGAM<\/jats:italic>\n , and members of the C1q family.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Macroscopic adenomatous polyp burden and growth dynamics were comparable across genotypes. However,\n \n APC\n 1311\/+<\/jats:sup>\n <\/jats:italic>\n \/\n \n TP53\n -\/-<\/jats:sup>\n <\/jats:italic>\n pigs exhibited significantly reduced epithelial proliferation within polyp crypts, as indicated by decreased Ki67\n +<\/jats:sup>\n expression. Furthermore, immunohistochemistry revealed a significant reduction of stromal IBA1\n +<\/jats:sup>\n macrophage\/monocyte-like cells in polyps from\n \n APC\n 1311\/+<\/jats:sup>\n <\/jats:italic>\n \/\n \n TP53\n -\/-<\/jats:sup>\n <\/jats:italic>\n animals. Consistently, expression levels of\n CCL2<\/jats:italic>\n ,\n ITGAM<\/jats:italic>\n ,\n FCGR3A<\/jats:italic>\n , and complement components\n C1QB<\/jats:italic>\n and\n C1QC<\/jats:italic>\n were significantly downregulated.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Loss of\n TP53<\/jats:italic>\n did not accelerate early-stage adenomatous polyp progression in the FAP pig model. However,\n TP53<\/jats:italic>\n deficiency was associated with significant alterations in the polyp microenvironment, particularly characterized by reduced C1q-associated macrophage remodeling and diminished expression of macrophage\/monocyte- and complement-related genes. These findings suggest a role for\n TP53<\/jats:italic>\n in modulating the inflammatory tumor microenvironment during colorectal tumorigenesis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1837646","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:15Z","timestamp":1783916595000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TP53 loss attenuates C1q-associated macrophage remodeling in early adenomatous polyps in a porcine FAP model"],"prefix":"10.3389","volume":"17","author":[{"given":"Qixia","family":"Chan","sequence":"first","affiliation":[{"name":"Chair of Infection Pathogenesis, School of Life Science, Technical University of Munich","place":["Freising, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liang","sequence":"additional","affiliation":[{"name":"Chair of Infection Pathogenesis, School of Life Science, 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