Fig. 1

VISTA functions non-redundantly to NCRs currently targeted in clinic. Each NCR occupies distinct temporal and spatial opportunities for blockade to release T cell suppression: [1] VISTA, as a receptor on T cells inhibit early T cell activation while [2] CTLA-4/CD80-86 interaction inhibit post-TCR signaling in secondary lymphoid organs. [3] PD-1/PD-L1 interaction inhibits effector T cells in inflamed tumor tissue. [4] VISTA, as a ligand on MDSCs engages counter structure to inhibit T cells in tumor tissue and secondary lymphoid organs