V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA)

V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA), also known as VSIR or B7-H5, is a type I transmembrane protein that functions as a potent negative checkpoint regulator within the B7 family (UniProt Q9H7M9). Unlike other checkpoints like PD-L1, VISTA is highly expressed on myeloid cells, including macrophages and dendritic cells, and acts to maintain T-cell quiescence and suppress inflammatory responses (PMID: 21383057). In the context of oncology, VISTA is frequently upregulated in the tumor microenvironment, where it contributes to immune evasion by inhibiting T-cell activation and promoting the suppressive activity of myeloid-derived suppressor cells (PMID: 31934165). Because its expression is often independent of the PD-1/PD-L1 pathway, VISTA is a critical target for overcoming resistance to current immunotherapies. Clinical development focuses on antagonistic antibodies such as CI-8993 and SNS-101, which aim to block VISTA's inhibitory signals and enhance anti-tumor immunity, though managing cytokine-related side effects remains a significant therapeutic challenge (NCT02671955, NCT04475523).

Other names

VSIRB7-H5GI24Dies1SISP1C10orf54Platelet receptor Gi24V-set immunoregulatory receptor

Antagonistic monoclonal antibodies block VISTA inhibitory signaling to restore T-cell anti-tumor activity; small molecule dual inhibitors target VISTA and PD-L1 pathways simultaneously.