{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:26:39Z","timestamp":1793499999387,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Else Kr\u00f6ner-Fresenius-Stiftung","award":["SE2980\/5-1"],"award-info":[{"award-number":["SE2980\/5-1"]}]},{"name":"The Ernst-Jung Stiftung","award":["SE2980\/5-1"],"award-info":[{"award-number":["SE2980\/5-1"]}]},{"name":"The Monika Kutzner Stiftung","award":["SE2980\/5-1"],"award-info":[{"award-number":["SE2980\/5-1"]}]},{"DOI":"10.13039\/501100001659","name":"The German Research Foundation","doi-asserted-by":"publisher","award":["SE2980\/5-1"],"award-info":[{"award-number":["SE2980\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Else Kr\u00f6ner Foundation","award":["SE2980\/5-1"],"award-info":[{"award-number":["SE2980\/5-1"]}]},{"name":"The German Cancer Consortium (DKTK)","award":["SE2980\/5-1"],"award-info":[{"award-number":["SE2980\/5-1"]}]},{"name":"The Medical Faculty Carl Gustav Carus TU Dresden","award":["SE2980\/5-1"],"award-info":[{"award-number":["SE2980\/5-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immunotherapy has shown promising results in multiple solid tumors and hematological malignancies. However, pancreatic ductal adenocarcinoma (PDAC) has been largely refractory to current clinical immunotherapies. The V-domain Ig suppressor of T-cell activation (VISTA) inhibits T-cell effector function and maintains peripheral tolerance. Here, we determine VISTA expression in nontumorous pancreatic (n = 5) and PDAC tissue using immunohistochemistry (n = 76) and multiplex immunofluorescence staining (n = 67). Additionally, VISTA expression on tumor-infiltrating immune cells and matched blood samples (n = 13) was measured with multicolor flow cytometry. Further, the effect of recombinant VISTA on T-cell activation was investigated in vitro, and VISTA blockade was tested in an orthotopic PDAC mouse model in vivo. PDAC showed significantly higher VISTA expression compared to that of a nontumorous pancreas. Patients with a high density of VISTA-expressing tumor cells had reduced overall survival. The VISTA expression of CD4+ and CD8+ T cells was increased after stimulation and particularly after a coculture with tumor cells. We detected a higher level of proinflammatory cytokine (TNF\u03b1 and IFN\u03b3) expression by CD4+ and CD8+ T cells, which was reversed with the addition of recombinant VISTA. A VISTA blockade reduced tumor weights in vivo. The VISTA expression of tumor cells has clinical relevance, and its blockade may be a promising immunotherapeutic strategy for PDAC.<\/jats:p>","DOI":"10.3390\/cancers15082326","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T02:02:59Z","timestamp":1681696979000},"page":"2326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["VISTA Ligation Reduces Antitumor T-Cell Activity in Pancreatic Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2139-9183","authenticated-orcid":false,"given":"David","family":"Digomann","sequence":"first","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Strack","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7907-4162","authenticated-orcid":false,"given":"Max","family":"Heiduk","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"National Center for Tumor Diseases (NCT\/UCC), 01307 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Plesca","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6610-326X","authenticated-orcid":false,"given":"Luise","family":"Rupp","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Reiche","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Nicolaus","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Beer","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Sommer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Schmitz","sequence":"additional","affiliation":[{"name":"National Center for Tumor Diseases (NCT\/UCC), 01307 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"},{"name":"Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Distler","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"National Center for Tumor Diseases (NCT\/UCC), 01307 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Weitz","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"National Center for Tumor Diseases (NCT\/UCC), 01307 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5329-3164","authenticated-orcid":false,"given":"Adrian M.","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"National Center for Tumor Diseases (NCT\/UCC), 01307 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-8127","authenticated-orcid":false,"given":"Lena","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"National Center for Tumor Diseases (NCT\/UCC), 01307 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, 69120 Heidelberg, Germany"},{"name":"Else Kr\u00f6ner Clinician Scientist Professor for \u201cTranslational Tumor Immunological Research\u201d, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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