{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:52:03Z","timestamp":1790628723503,"version":"4.1.0"},"reference-count":93,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T00:00:00Z","timestamp":1588723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WE3559\/6-1"],"award-info":[{"award-number":["WE3559\/6-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Faculty of the UKSH, Kiel, Germany","award":["MD fellowship of H.J."],"award-info":[{"award-number":["MD fellowship of H.J."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Pancreatic ductal adenocarcinoma (PDAC) is a malignant gastrointestinal disease. The enzyme indoleamine-2,3-dioxgenase (IDO) is often overexpressed in PDAC and its downstream metabolite kynurenine has been reported to inhibit T cell activation and proliferation. Since \u03b3\u03b4 T cells are of high interest for T cell-based immunotherapy against PDAC, we studied the impact of IDO and kynurenine on \u03b3\u03b4 T cell cytotoxicity against PDAC cells. Methods: IDO expression was determined in PDAC cells by flow cytometry and Western blot analysis. PDAC cells were cocultured with \u03b3\u03b4 T cells in medium or were stimulated with phosphorylated antigens or bispecific antibody in the presence or absence of IDO inhibitors. Additionally, \u03b3\u03b4 T cells were treated with recombinant kynurenine. Read-out assays included degranulation, cytotoxicity and cytokine measurement as well as cell cycle analysis. Results: Since IDO overexpression was variable in PDAC, IDO inhibitors improved \u03b3\u03b4 T cell cytotoxicity only against some but not all PDAC cells. \u03b3\u03b4 T cell degranulation and cytotoxicity were significantly decreased after their treatment with recombinant kynurenine. Conclusions: Bispecific antibody drastically enhanced \u03b3\u03b4 T cell cytotoxicity against all PDAC cells, which can be further enhanced by IDO inhibitors against several PDAC cells, suggesting a striking heterogeneity in PDAC escape mechanisms towards \u03b3\u03b4 T cell-mediated anti-tumor response.<\/jats:p>","DOI":"10.3390\/cells9051140","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T04:46:07Z","timestamp":1588826767000},"page":"1140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Influence of Indoleamine-2,3-Dioxygenase and Its Metabolite Kynurenine on \u03b3\u03b4 T Cell Cytotoxicity against Ductal Pancreatic Adenocarcinoma Cells"],"prefix":"10.3390","volume":"9","author":[{"given":"Hannah","family":"Jonescheit","sequence":"first","affiliation":[{"name":"Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Heinrich","family":"Oberg","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gonnermann","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hermes","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vjola","family":"Sulaj","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7669-3806","authenticated-orcid":false,"given":"Christian","family":"Peters","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4160-7103","authenticated-orcid":false,"given":"Dieter","family":"Kabelitz","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Wesch","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9694","DOI":"10.3748\/wjg.v22.i44.9694","article-title":"Epidemiology of pancreatic cancer","volume":"22","author":"Ilic","year":"2016","journal-title":"World J. 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