V-set immunoregulatory receptor (VISTA) (VISTA)

V-set immunoregulatory receptor (VISTA) is a type I transmembrane protein and a member of the B7 family of immune checkpoint molecules that plays a critical role in maintaining peripheral tolerance (UniProt Q9H7M9). It is primarily expressed on myeloid cells, such as macrophages and dendritic cells, and is also found on T-lymphocytes, where it functions as a potent negative regulator of T-cell activation and cytokine production (Wang et al., 2011, PubMed: 21383057). In the tumor microenvironment, VISTA is often upregulated, contributing to immune evasion by suppressing anti-tumor T-cell responses and promoting the activity of myeloid-derived suppressor cells (Lines et al., 2014, PubMed: 24691993). Unlike other checkpoints like PD-1, VISTA's expression is frequently maintained or increased following treatment with other immunotherapies, making it a significant target for overcoming resistance in various cancers (Nowak et al., 2017, PubMed: 28923825). Therapeutic strategies currently focus on monoclonal antibodies designed to block VISTA's inhibitory signaling to enhance immune-mediated tumor clearance (ClinicalTrials.gov NCT02671955). Additionally, VISTA agonists are being explored for the treatment of autoimmune and inflammatory diseases to restore immune tolerance (ElTanbouly et al., 2020, PubMed: 32051256). A unique feature of VISTA is its pH-sensitive binding, which is being leveraged in drug design to target the acidic tumor microenvironment specifically (Johnston et al., 2019, PubMed: 31645450).

Other names

V-domain Ig suppressor of T-cell activationB7-H5GI24Dies1SISP1PD-1HVSIRPlatelet receptor Gi24

Immune checkpoint inhibition (antagonism) to enhance T-cell activity against tumors; Immune checkpoint activation (agonism) to suppress overactive immune responses in autoimmunity.