VISTA (protein)
V-domain Ig suppressor of T cell activation is a type I transmembrane protein that functions as an immune checkpoint and is encoded by the VSIR gene.
Structure and function
VISTA is approximately 50 kDa and belongs to the immunoglobulin superfamily and has one IgV domain.VISTA is part of the B7 family, is primarily expressed in white blood cells and its transcription is partially controlled by p53. There is evidence that VISTA can act as a ligand that engages an inhibitory receptor LRIG1 on T cells and impairs T cell activation and function.
Another binding partner for VISTA is PSGL-1, which binds VISTA only under acidic conditions. VISTA expressed on T cells also intrinsically suppresses T cell activation, likely by engaging other inhibitory receptors on the same cell. Aside from T cells, VISTA is highly expressed on macrophages and myeloid-derived suppressor cells and regulates their differentiation and function. Similarly, VISTA and TIM-3 may co-exist on macrophages infiltrating different human and mouse tumours where they can co-regulate immunotherapy resistance.
Clinical significance
VISTA is expressed at high levels in tumor-infiltrating lymphocytes, such as myeloid-derived suppressor cells and regulatory T cells, and its blockade with an [Monoclonal Monoclonal antibody therapy|antibody therapy|antibody] results in delayed tumor growth in mouse models of melanoma and squamous cell carcinoma. It is also up-regulated in tumour-associated macrophages in various malignancies, including melanoma, especially in immunotherapy-resistant human context.VISTA cooperates with another immune checkpoint receptor PD-1 in modulating anti-tumor immunity and autoimmunity.
Monocytes from HIV-infected patients produce higher levels of VISTA compared to uninfected individuals. The increased VISTA levels correlated with an increase in immune activation and a decrease in CD4-positive T cells.