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. 2022 Nov 30;23(23):15005. doi: 10.3390/ijms232315005

Figure 4.

Figure 4

VISTA expression regulation and function in PDAC. VISTA is primarily expressed in tumor-infiltrating immune cells. Hypoxic TME stimulates VISTA expression via upregulation of HIF-1α, while VISTA is a direct downstream target of reactive p53 molecules. Expression of VISTA may be positively correlated with TLR-4. VISTA can act as a receptor and ligand, binding to several cells and substances in the TME. When serving as a receptor, VISTA binds to the ligand in a pH-dependent manner. VISTA attaches to PSGL-1 on T cells at a pH of about 6.0. When the pH rises to about 7.4, VISTA binds selectively to VSIG-3 on tumor cells, blocking the synthesis of chemicals including IL-2, IL-17, and CCL5. As a ligand, VISTA-Ig greatly increased the conversion of naive T cells into Foxp3+ T cells while suppressing the proliferation of CD4/CD8 T cells, lowering IFN-γ, TNF-α and IL-2 production. The connection between VISTA-VISTA-IgV structural domains on the surface of macrophages and apoptotic cells may facilitate the prompt clearance of apoptotic cells.