VISTA/B7-H5/PD-1H: Proteins and Enzymes

VISTA (V-domain immunoglobulin suppressor of T cell activation) is a cell surface coinhibitory protein belonging to the CD28/B7 family. VISTA can act as both a ligand and a receptor in regulating T cell activity. VISTA is expressed on dendritic cells, monocytes, and both CD4+ and CD8+ T cells. VISTA functions as an inhibitory receptor downregulating CD4+ and CD8+ T cell proliferation and exhibiting a protective effect in mice from graft versus host disease, asthma, and acute hepatitis.

VISTA also acts as a ligand on antigen presenting cells. Two cell surface expressed proteins VSIG-3 and PSGL-1 have been identified as binding partners of VISTA. Immune checkpoint proteins like the VISTA protein are often overexpressed by cancer cells or surrounding cells in the tumor microenvironment. VISTA upregulation occurs on tumor-infiltrating leukocytes and is expressed on several cancer types including melanoma, lung, ovarian, colon, prostate, and pancreatic cancer. Further, knockout and blocking antibody studies of VISTA have shown an increase in T cell responses in several mouse tumor models making VISTA a potential therapeutic target alone or in combination with other known immune checkpoint inhibitors. Alternative names of VISTA include PD-1H, Gi24, Dies1, and SISP1.