TY  - JOUR
AU  - Digomann, David
AU  - Strack, Johannes
AU  - Heiduk, Max
AU  - Plesca, Ioana
AU  - Rupp, Luise
AU  - Reiche, Charlotte
AU  - Nicolaus, Simone
AU  - Beer, Carolin
AU  - Sommer, Ulrich
AU  - Schmitz, Marc
AU  - Distler, Marius
AU  - Weitz, Jürgen
AU  - Seifert, Adrian M
AU  - Seifert, Lena
TI  - VISTA Ligation Reduces Antitumor T-Cell Activity in Pancreatic Cancer.
JO  - Cancers
VL  - 15
IS  - 8
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2023-00961
SP  - 2326
PY  - 2023
AB  - 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.
KW  - VISTA (Other)
KW  - cytokines (Other)
KW  - pancreatic cancer (Other)
KW  - prognosis (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37190254
DO  - DOI:10.3390/cancers15082326
UR  - https://inrepo02.dkfz.de/record/276055
ER  -