V-domain Ig suppressor of T cell activation (VISTA) (VISTA)

V-domain Ig suppressor of T cell activation (VISTA) is a B7 family immune checkpoint protein that functions as a potent negative regulator of T-cell-mediated immunity (Yuan et al., Trends in Cancer, 2021). It is primarily expressed on myeloid cells and T lymphocytes, where it plays a critical role in maintaining peripheral tolerance and preventing autoimmunity. A defining feature of VISTA biology is its pH-dependent interaction with P-selectin glycoprotein ligand-1 (PSGL-1), which serves as a primary receptor for VISTA specifically under the acidic conditions (pH ~6.0) characteristic of the tumor microenvironment (Johnston et al., Nature, 2019). This binding at the VISTA/PSGL-1 interface triggers inhibitory signaling that suppresses T-cell proliferation and cytokine production, thereby facilitating tumor immune escape. Because this interaction is largely restricted to acidic environments, it represents a highly specific therapeutic target for oncology. Therapeutic strategies targeting this interface, such as the pH-selective antibody SNS-101, aim to restore anti-tumor immune responses while minimizing systemic side effects like cytokine release syndrome (Rogers et al., Cancer Immunol Res, 2023). This approach allows for potentially higher dosing and improved safety compared to non-selective VISTA blockade.

Other names

VSIRB7-H5Dies1Gi24SISP1Platelet receptor Gi24V-set immunoregulatory receptor

Immune checkpoint inhibition by blocking the pH-dependent interaction between VISTA and its receptors, such as PSGL-1, to prevent T-cell suppression and restore anti-tumor immunity (Johnston et al., Nature, 2019).