{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T16:04:44Z","timestamp":1779552284340,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,20]]},"group-title":"Cancer Biology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RO1CA237304"],"award-info":[{"award-number":["RO1CA237304"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U01CA214300"],"award-info":[{"award-number":["U01CA214300"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007311","name":"Cleveland Clinic","doi-asserted-by":"crossref","award":["Cleveland Clinic Catalyst"],"award-info":[{"award-number":["Cleveland Clinic Catalyst"]}],"id":[{"id":"10.13039\/100007311","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>\n                  <jats:bold>ABSTRACT<\/jats:bold>\n                <\/jats:title>\n                <jats:p>\n                  Ulcerative colitis is a chronic inflammatory bowel disease that can progress from dysplasia to cancer. Inflammatory responses are critical drivers in this process, typically triggered by epithelial lesions and the ensuing infiltration of microbiota into the interstitial layer. Here, we focus on the pro-inflammatory state of the interstitial fibroblasts, which promotes immune infiltration and augments disease progression. The study aims to provide a mechanistic link how fibroblasts of the colitis-associated microenvironment integrate inflammatory signals, microbial infiltration and cellular memory. To this end, we investigated a large number of primary colon fibroblasts obtained from normal, colitis and colon cancer samples using a range of\n                  <jats:italic>in vitro<\/jats:italic>\n                  approaches and an\n                  <jats:italic>in vivo<\/jats:italic>\n                  co-inoculation cancer model. mRNA sequencing analysis identified that the disease-associated fibroblasts are exhibit a cellular inflammatory status, which involves the injury-induced senescence pathway. Using CXCL8, a potent chemokine upregulated in colitis and cancer colon fibroblasts, as a paradigm, this inflammatory status is triggered by the activation of the NF\u03baB signaling via immune-derived cytokines (TNF\u03b1, IL-1\u03b2), bacterial signals (LPS) and the microbiome itself using mycoplasma as a paradigm. Finally, iPSC reprogramming studies indicate that fibroblasts from ulcerative colitis retain an epigenetic memory that sustains elevated CXCL8 expression. Together, our findings demonstrate that the senescence associated secretory phenotype of colon fibroblasts is a robust indicator for inflammation-driven colon tumorigenesis.\n                <\/jats:p>","DOI":"10.64898\/2026.05.18.725891","type":"posted-content","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:15:15Z","timestamp":1779293715000},"source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Stromal Aging in Ulcerative Colitis and Colitis-Associated Cancer"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2456-5528","authenticated-orcid":false,"given":"Khalil","family":"Almotah","sequence":"first","affiliation":[{"name":"Dept. Cardiovascular & Metabolic Sciences, Cleveland Clinic Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland OH 44195"},{"name":"Dept. 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Inflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland OH 44195"},{"name":"Dept. of Surgery, UT Southwestern Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390"},{"name":"Simmons Comprehensive Cancer Center, University of Texas Southwestern, 5323 Harry Hines Boulevard, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaroslav","family":"Bisikalo","sequence":"additional","affiliation":[{"name":"Dept. of Surgery, UT Southwestern Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390"},{"name":"Simmons Comprehensive Cancer Center, University of Texas Southwestern, 5323 Harry Hines Boulevard, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"Ali","sequence":"additional","affiliation":[{"name":"Dept. of Surgery, UT Southwestern Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390"},{"name":"Simmons Comprehensive Cancer Center, University of Texas Southwestern, 5323 Harry Hines Boulevard, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munir","family":"Buhaya","sequence":"additional","affiliation":[{"name":"Dept. of Surgery, UT Southwestern Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390"},{"name":"Simmons Comprehensive Cancer Center, University of Texas Southwestern, 5323 Harry Hines Boulevard, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Dept. of Surgery, UT Southwestern Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cruise","sequence":"additional","affiliation":[{"name":"Dept. of Pathology, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland OH 44195"},{"name":"Dept. of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikai","family":"Chi","sequence":"additional","affiliation":[{"name":"Simmons Comprehensive Cancer Center, University of Texas Southwestern, 5323 Harry Hines Boulevard, Dallas, TX 75390"},{"name":"Dept. of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaneh Kamali","family":"Sarvestani","sequence":"additional","affiliation":[{"name":"Dept. 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