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@ARTICLE{Digomann:276055,
      author       = {D. Digomann and J. Strack and M. Heiduk and I. Plesca and
                      L. Rupp and C. Reiche and S. Nicolaus and C. Beer and U.
                      Sommer and M. Schmitz$^*$ and M. Distler$^*$ and J.
                      Weitz$^*$ and A. M. Seifert$^*$ and L. Seifert$^*$},
      title        = {{VISTA} {L}igation {R}educes {A}ntitumor {T}-{C}ell
                      {A}ctivity in {P}ancreatic {C}ancer.},
      journal      = {Cancers},
      volume       = {15},
      number       = {8},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-00961},
      pages        = {2326},
      year         = {2023},
      abstract     = {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.},
      keywords     = {VISTA (Other) / cytokines (Other) / pancreatic cancer
                      (Other) / prognosis (Other)},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37190254},
      doi          = {10.3390/cancers15082326},
      url          = {https://inrepo02.dkfz.de/record/276055},
}