{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T08:44:08Z","timestamp":1792485848864,"version":"4.5.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Cholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells of intra\u2010 and extrahepatic bile ducts with dismal prognosis and few nonsurgical treatments available. Despite recent success in the immunotherapy\u2010based treatment of many tumor types, this has not been successfully translated to CCA. Mucosal\u2010associated invariant T (MAIT) cells are cytotoxic innate\u2010like T cells highly enriched in the human liver, where they are located in close proximity to the biliary epithelium. Here, we aimed to comprehensively characterize MAIT cells in intrahepatic (iCCA) and perihilar CCA (pCCA).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Liver tissue from patients with CCA was used to study immune cells, including MAIT cells, in tumor\u2010affected and surrounding tissue by immunohistochemistry, RNA\u2010sequencing, and multicolor flow cytometry. The iCCA and pCCA tumor microenvironment was characterized by the presence of both cytotoxic T cells and high numbers of regulatory T cells. In contrast, MAIT cells were heterogenously lost from tumors compared to the surrounding liver tissue. This loss possibly occurred in response to increased bacterial burden within tumors. The residual intratumoral MAIT cell population exhibited phenotypic and transcriptomic alterations, but a preserved receptor repertoire for interaction with tumor cells. Finally, the high presence of MAIT cells in livers of iCCA patients predicted long\u2010term survival in two independent cohorts and was associated with a favorable antitumor immune signature.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>MAIT cell tumor infiltration associates with favorable immunological fitness and predicts survival in CCA.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32222","type":"journal-article","created":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T14:42:29Z","timestamp":1635604949000},"page":"1154-1168","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":39,"title":["Mucosal\u2010associated invariant T\u2010cell tumor infiltration predicts long\u2010term survival in cholangiocarcinoma"],"prefix":"10.1097","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7240-6622","authenticated-orcid":false,"given":"Christine L.","family":"Zimmer","sequence":"first","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8166-5500","authenticated-orcid":false,"given":"Iva","family":"Filipovic","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Cornillet","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colm J.","family":"O\u2019Rourke","sequence":"additional","affiliation":[{"name":"Biotech Research and Innovation Centre (BRIC),Department of Health and Medical Sciences,University of Copenhagen,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Berglin","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Jansson","sequence":"additional","affiliation":[{"name":"Division of Surgery,Department of Clinical Science, Intervention and Technology,Karolinska Institutet,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Strauss","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hertwig","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Johansson","sequence":"additional","affiliation":[{"name":"Division of Transplantation Surgery,CLINTEC,Karolinka Institutet and Department of Transplantation,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"von Seth","sequence":"additional","affiliation":[{"name":"Division of Upper GI Diseases,Karolinska University Hospital,Stockholm,Sweden"},{"name":"Unit of Gastroenterology and Rheumatology,Department of Medicine Huddinge,Karolinska Institutet,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Sparrelid","sequence":"additional","affiliation":[{"name":"Division of Surgery,Department of Clinical Science, Intervention and Technology,Karolinska Institutet,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Dias","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Glaumann","sequence":"additional","affiliation":[{"name":"Department of Medicine,Clinical Pathology and Cytology,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6903-6878","authenticated-orcid":false,"given":"Espen","family":"Melum","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center,Department of Transplantation Medicine,Division of Surgery,Inflammatory Diseases and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine,Division of Surgery,Inflammatory Diseases and Transplantation,Oslo University Hospital,Oslo,Norway"},{"name":"Institute of Clinical Medicine,Faculty of Medicine,University of Oslo,Oslo,Norway"},{"name":"Section of Gastroenterology,Department of Transplantation Medicine,Division of Surgery,Inflammatory Diseases and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"Hybrid Technology Hub\u2010Centre of Excellence,Institute of Basic Medical Sciences,Faculty of Medicine,University of Oslo,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3057-5337","authenticated-orcid":false,"given":"Ewa C.","family":"Ellis","sequence":"additional","affiliation":[{"name":"Division of Transplantation Surgery,CLINTEC,Karolinka Institutet and Department of Transplantation,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan K.","family":"Sandberg","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1760-5244","authenticated-orcid":false,"given":"Jesper B.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Biotech Research and Innovation Centre (BRIC),Department of Health and Medical Sciences,University of Copenhagen,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3858-6241","authenticated-orcid":false,"given":"Annika","family":"Bergquist","sequence":"additional","affiliation":[{"name":"Division of Upper GI Diseases,Karolinska University Hospital,Stockholm,Sweden"},{"name":"Unit of Gastroenterology and Rheumatology,Department of Medicine Huddinge,Karolinska Institutet,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0967-076X","authenticated-orcid":false,"given":"Niklas K.","family":"Bj\u00f6rkstr\u00f6m","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge,Karolinska Institutet, Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"hep32222-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1053\/j.gastro.2013.10.013","article-title":"Pathogenesis, diagnosis, and management of cholangiocarcinoma","volume":"145","year":"2013","journal-title":"Gastroenterology"},{"key":"hep32222-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: the next horizon in mechanisms and management","volume":"17","year":"2020","journal-title":"Nat Rev Gastroenterol 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through MR1","volume":"64","year":"2016","journal-title":"J Hepatol"},{"key":"hep32222-bib-0007-20250824","article-title":"MAIT cells detect and efficiently lyse bacterially\u2010infected epithelial cells","volume":"9","year":"2013","journal-title":"PLoS Pathog"},{"key":"hep32222-bib-0008-20250824","article-title":"Arming of MAIT cell cytolytic antimicrobial activity is induced by IL\u20107 and defective in HIV\u20101 infection","volume":"11","year":"2015","journal-title":"PLoS Pathog"},{"key":"hep32222-bib-0009-20250824","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/ni.1890","article-title":"Antimicrobial activity of mucosal\u2010associated invariant T cells","volume":"11","year":"2010","journal-title":"Nat Immunol"},{"key":"hep32222-bib-0010-20250824","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/eji.201343509","article-title":"CD161++ CD8+ T cells, including the MAIT cell subset, are specifically activated by IL\u201012+IL\u201018 in a 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