Abstract

V-domain Ig Suppressor of T cell Activation (VISTA) is a negative immune checkpoint that is expressed on multiple immune cell subsets and whose function has been characterized in T cells, macrophages, and myeloid-derived suppressor cells (MDSCs). VISTA is the only immune checkpoint expressed on naïve T cells and has a prominent role in maintaining T cell quiescence and tolerance. VISTA also regulates multiple myeloid cell activities such as chemotaxis, differentiation, and migration. VISTA is expressed in multiple types of cancers, particularly in immune cell infiltrates, and murine models using an antagonistic monoclonal antibody targeting VISTA to improve anti-tumor immunity. Furthermore, combination therapies that include VISTA blockade may enhance therapeutic efficacy in a variety of cancers, especially in cases of adaptive resistance, and improve patient outcomes and survival. Here, we summarize the role of VISTA across multiple immune cell subsets, particularly in myeloid cells and T cells in the tumor microenvironment. We discuss the proposed counter-receptors for VISTA, VISTA antibodies currently in development, and the potential for combination therapies with checkpoint inhibitors such as PD-1 and CTLA-4.