%0 Journal Article
%A Digomann, David
%A Strack, Johannes
%A Heiduk, Max
%A Plesca, Ioana
%A Rupp, Luise
%A Reiche, Charlotte
%A Nicolaus, Simone
%A Beer, Carolin
%A Sommer, Ulrich
%A Schmitz, Marc
%A Distler, Marius
%A Weitz, Jürgen
%A Seifert, Adrian M
%A Seifert, Lena
%T VISTA Ligation Reduces Antitumor T-Cell Activity in Pancreatic Cancer.
%J Cancers
%V 15
%N 8
%@ 2072-6694
%C Basel
%I MDPI
%M DKFZ-2023-00961
%P 2326
%D 2023
%X 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 (TNFα and IFNγ) 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.
%K VISTA (Other)
%K cytokines (Other)
%K pancreatic cancer (Other)
%K prognosis (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37190254
%R 10.3390/cancers15082326
%U https://inrepo02.dkfz.de/record/276055