Fig. 3

The effect of VISTA interaction with ligands and their binding effects. a The interaction between VSIG-3 and VSIG-8 expressed within tumor cells with VISTA on T cells causes inhibition in T cell activation and proliferation, reduction in IFN-γ, IL-2, IL-17, CCL3, CCL5, CXCL11 production, and suppression of immune cell infiltration to the TME. b The binding of Gal-9 secreted from the AML cells to VISTA expressed on T cells induces apoptosis in activated T cells and inhibits immune responses in the TME. c The interaction between PSGL-1 expressed on T cells with VISTA expressed on tumor cells, TILs, and TAMs/MDSCs not only suppresses T cell activation (blocking NF-κB pathway and reduction in IFN-γ production) and proliferation but also decreases the production of anti-inflammatory mediators in TME. d The MMP-13 produced by MM tumor cells binds to the VISTA expressed on the osteoclasts and T cells, causing bone resorption and T cell suppression, respectively. e The binding of VISTA to its unidentified ligand on monocyte surfaces is associated with Sdc-2 interactions, which have an impact on monocyte biological functions. VISTA (V-domain immunoglobulin suppressor of T cell activation), VSIG-3 (V-Set and Immunoglobulin domain containing 3, VSIG-8 (V-Set and Immunoglobulin domain containing 8), PSGL-1 (P-selectin glycoprotein ligand-1), Gal-9 (Galectin-9), MMP-13 (matrix metalloproteinase-13), Sdc2 (syndecan-2), IFN-γ (interferon gamma), TNF (tumor necrosis factor), NF-κB (nuclear factor kappa B), IL (interleukin), CCL3 (chemokine (C–C motif) ligand 3), CCL5 (chemokine (C–C motif) ligand 5), CXCL11 (C-X-C motif chemokine 11), Cas-3 (caspase 3), TAMs (tumor-associated macrophages), MDSCs (myeloid-derived suppressor cells), TME (tumor microenvironment), AML (acute myeloid leukemia), MM (multiple myeloma). Created with BioRender.com