{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:46:34Z","timestamp":1783698394729,"version":"3.55.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Fistula formation is a common and debilitating complication in Crohn\u2019s disease (CD). CD-associated fistula carcinomas (Fi-Cas), though rare, pose diagnostic and prognostic challenges. This study aims to identify disease-defining immune cell subsets in CD-associated Fi-Cas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The study included tissue samples from 10 CD patients with Fi-Cas, 7 with CD-associated fistulas, and 6 with sporadic colorectal cancer (CRC). The main tumor (MT), infiltration front, and non-involved areas were analyzed in tumor samples. A 36-marker panel was employed to define the immune landscape using imaging mass cytometry. Samples were processed, stained, and analyzed for immune cell compositions, cell-cell interactions, and spatial microenvironments.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The immune infiltrate in Fi-Cas shared similarities with both CD fistulas and CRC. Fi-Ca samples exhibited high levels of neutrophils, B cells, and CD163high macrophages. CRC MT samples showed an increased presence of intraepithelial CD8+ lymphocytes and CD163low macrophages. Cleaved Caspase-3 levels were highest in CRC MT samples, correlating positively with CD163low macrophages and cytotoxic T cells. In contrast, Fi-Ca MT samples showed a negative correlation between cleaved Caspase-3 and cytotoxic T cells. Analysis of cellular microenvironments and dimensionality reduction clustering based on immune cell frequencies indicated Fi-Cas to exhibit a mixture of immune cell characteristics from both CD fistulas and CRC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The immune landscape of CD-associated Fi-Cas exhibits features of both CD fistulas and CRC, suggesting a complex pathogenesis influenced by chronic inflammation. Our data suggest that Fi-Cas represent a unique cancer subtype, that requires further analysis to develop targeted therapeutic strategies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaf086","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T08:08:46Z","timestamp":1748246926000},"source":"Crossref","is-referenced-by-count":1,"title":["Spatial immune profiling of Crohn\u2019s disease fistula carcinomas\u2014defining a distinct cancer subtype"],"prefix":"10.1093","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3786-7375","authenticated-orcid":false,"given":"Malte","family":"Lehmann","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Berlin 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