{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:29:08Z","timestamp":1785414548546,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,4]]},"group-title":"Immunology","reference-count":77,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]},{"name":"NIH","award":["R01DK113375"],"award-info":[{"award-number":["R01DK113375"]}]},{"name":"NIH","award":["R01DK093674"],"award-info":[{"award-number":["R01DK093674"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Colorectal cancer (CRC) remains a leading cause of cancer mortality, with most cases refractory to immunotherapy. Distinguishing tumor-induced from steady-state mucosal T cell responses has been a critical barrier to understanding antitumor immunity in CRC. Using orthotopic transplantation of CRC organoids with and without metastatic potential, combined with temporal T cell fate-mapping, we show that non-metastatic tumors elicit early recruitment of CD8\u03b1\u03b2\u207a and CD4\u207a T cells that acquired cytotoxic and Th1-like programs, whereas pro-metastatic tumors induce a na\u00efve-like, hypoactivated state. Tumor-infiltrating CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells underwent clonal expansion, including clones recognizing microbial and dietary antigens. T cells in physical contact with tumor cells, identified by uLIPSTIC, were enriched for expanded and cytotoxic clones. Fate-mapped T cells from non-metastatic tumors suppressed tumor growth in an IFN-\u03b3-dependent manner, whereas pro-metastatic tumor-derived T cells failed to do so. Mechanistically, pro-metastatic tumors downregulated MHCII, and\n                  <jats:italic>Ciita<\/jats:italic>\n                  targeting in non-metastatic organoids reduced CD4\u207a clonal expansion and led to tumor progression. Together, these findings define divergent early T cell trajectories associated with CRC metastatic potential, indicating that ineffective local immune engagement precedes metastatic dissemination.\n                <\/jats:p>","DOI":"10.64898\/2026.06.30.735606","type":"posted-content","created":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T04:40:12Z","timestamp":1783226412000},"source":"Crossref","is-referenced-by-count":0,"title":["Colorectal cancers with distinct metastatic potential trigger divergent early T cell responses"],"prefix":"10.64898","author":[{"given":"Marwa","family":"Saad","sequence":"first","affiliation":[{"name":"Laboratory of Mucosal Immunology, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Thoms","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue S.","family":"Yin","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Mamede","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afsana","family":"Rahman","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruonan","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n E.","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Pathology, Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center and Rockefeller University, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W.","family":"Darcy","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Goto","sequence":"additional","affiliation":[{"name":"The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohail F.","family":"Tavazoie","sequence":"additional","affiliation":[{"name":"Laboratory of Systems Cancer Biology, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4575-786X","authenticated-orcid":false,"given":"Angelina M.","family":"Bilate","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0000-0452","authenticated-orcid":false,"given":"Daniel","family":"Mucida","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Immunology, The Rockefeller University, New York, United States"},{"name":"Howard Hughes Medical Institute, The Rockefeller University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070805250566000_2026.06.30.735606v1.1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20162014"},{"key":"2026070805250566000_2026.06.30.735606v1.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-090222-100246"},{"key":"2026070805250566000_2026.06.30.735606v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(19)32319-0"},{"key":"2026070805250566000_2026.06.30.735606v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0189-8"},{"key":"2026070805250566000_2026.06.30.735606v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-024-00934-z"},{"key":"2026070805250566000_2026.06.30.735606v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90186-I"},{"key":"2026070805250566000_2026.06.30.735606v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature11252"},{"key":"2026070805250566000_2026.06.30.735606v1.8","first-page":"609","article-title":"Systematic Review of Microsatellite Instability and Colorectal Cancer Prognosis","volume":"23","year":"2004","journal-title":"J. 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