{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:35:34Z","timestamp":1790634934919,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The occurrence of peritoneal metastasis (PM) in patients with colorectal cancer (CRC) has a dismal prognosis. There is often limited response to systemic- and immunotherapy, even in microsatellite unstable (MSI) CRC. To overcome therapy resistance, it is critical to understand local immune environment in the peritoneal cavity, and to develop models to study anti-tumor immune responses. Here, we defined the peritoneal immune system (PerIS) in PM-CRC patients and evaluate the pre-clinical potential of a humanized immune system (HIS) mouse model for PM-CRC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied the human PerIS in PM-CRC patients (n=20; MSS 19\/20; 95%) and in healthy controls (n=3). HIS mice (NODscid gamma background; n=18) were generated, followed by intraperitoneal injection of either saline (HIS control; n=3) or human MSS\/MSI CRC cell lines HUTU80, MDST8 and HCT116 (HIS-PM, n=15). Immune cells in peritoneal fluid and peritoneal tumors were analyzed using cytometry by time of flight (CyTOF).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The human and HIS mouse homeostatic PerIS was equally populated by NK cells and CD4+- and CD8+ T cells, however differences were observed in macrophage and B cell abundance. In HIS mice, successful peritoneal engraftment of both MSI and MSS tumors was observed (15\/15; 100%). Both in human PM-CRC and in the HIS mouse PM-CRC model, we observed that MSS PM-CRC triggered a CD4+ Treg response in the PerIS, while MSI PM-CRC drives CD8+ TEMs responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, T cell responses in PM-CRC in HIS mice mirror those in human PM-CRC, making this model suitable to study antitumor T cell responses in PM-CRC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1415457","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T04:59:15Z","timestamp":1720501155000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["T-cell responses in colorectal peritoneal metastases are recapitulated in a humanized immune system mouse model"],"prefix":"10.3389","volume":"15","author":[{"given":"Job","family":"Saris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"Bootsma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Verhoeff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurriaan B.","family":"Tuynman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon E.","family":"Wildenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther Siteur-van","family":"Rijnstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristiaan J.","family":"Lenos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Garcia Vallejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Vermeulen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joep","family":"Grootjans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30500-9","article-title":"Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database","volume":"17","author":"Franko","year":"2016","journal-title":"Lancet Oncol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4443","DOI":"10.1038\/s41467-022-32198-z","article-title":"Molecular characterization of colorectal cancer related peritoneal metastatic disease","volume":"13","author":"Lenos","year":"2022","journal-title":"Nat Commun"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-01742-5","article-title":"Peritoneal metastases from colorectal cancer belong to Consensus Molecular Subtype 4 and are sensitised to oxaliplatin by inhibiting reducing capacity","volume":"126","author":"Laoukili","year":"2022","journal-title":"Br J Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3967","article-title":"The consensus molecular subtypes of colorectal cancer","volume":"21","author":"Guinney","year":"2015","journal-title":"Nat Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0805-8","article-title":"Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers","volume":"26","author":"Chalabi","year":"2020","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2017699","article-title":"Pembrolizumab in microsatellite-instability-high advanced colorectal cancer","volume":"383","author":"Andr\u00e9","year":"2020","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.currproblcancer.2018.06.010","article-title":"The impact of microsatellite stability status in colorectal cancer","volume":"42","author":"Gupta","year":"2018","journal-title":"Curr Probl Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"101574","DOI":"10.1016\/j.esmoop.2023.101574","article-title":"Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. 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