VISTA (protein)

 V-domain Ig suppressor of T cell activation (VISTA) is a type I transmembrane protein that functions as an immune checkpoint and is encoded by the C10orf54 gene.^[5][6][7]

VSIR
Identifiers
Aliases	VSIR, B7-H5, B7H5, GI24, PP2135, SISP1, DD1alpha, VISTA, C10orf54, chromosome 10 open reading frame 54, PD-1H, V-set immunoregulatory receptor, Dies1
External IDs	OMIM: 615608 MGI: 1921298 HomoloGene: 81923 GeneCards: VSIR
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q22.1 Start 71,747,556 bp[1] End 71,773,520 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 B4 Start 60,346,851 bp[2] End 60,372,684 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • identical protein binding • enzyme binding • endopeptidase activator activity Cellular component • integral component of membrane • membrane • cell membrane Biological process • positive regulation of gene expression • positive regulation of endopeptidase activity • positive regulation of cell migration • zymogen activation • negative regulation of interferon-gamma production • negative regulation of interleukin-10 production • negative regulation of interleukin-17 production • negative regulation of tumor necrosis factor production • positive regulation of regulatory T cell differentiation • positive regulation of collagen catabolic process • negative regulation of CD4-positive, alpha-beta T cell proliferation • negative regulation of CD8-positive, alpha-beta T cell proliferation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	64115	74048
Ensembl	ENSG00000107738	ENSMUSG00000020101
UniProt	Q9H7M9	Q9D659
RefSeq (mRNA)	NM_022153	NM_001159572 NM_028732
RefSeq (protein)	NP_071436	NP_001153044 NP_083008
Location (UCSC)	Chr 10: 71.75 – 71.77 Mb	Chr 10: 60.35 – 60.37 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure and functionEdit

VISTA is approximately 50kDa and belongs to the immunoglobulin superfamily and has one IgV domain.^[8][5]

VISTA is part of the B7 family, is primarily expressed in white blood cells and its transcription is partially controlled by p53.^[8][9] There is evidence that VISTA can act as both a ligand^[10] and a receptor^[11] on T cells to inhibit T cell effector function and maintain peripheral tolerance.^[5][8]

Clinical significanceEdit

VISTA is produced at high levels in tumor-infiltrating lymphocytes, such as myeloid-derived suppressor cells and regulatory T cells, and its blockade with an antibody results in delayed tumor growth in mouse models of melanoma^[12] and squamous cell carcinoma.^[13]

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.^[14]

As a drug targetEdit

There is an ongoing cancer immunotherapy clinical trial for a monoclonal antibody targeting VISTA in advanced cancer.^[15] Preliminary results of the phase I clinical trial show good safety tolerance and anti-cancer activity in patients with advanced tumours.^[16] Another ongoing clinical trial involves a small molecule that antagonizes the programmed death-ligands 1 and 2 (PD-L1 and PD-L2), and VISTA pathways in patients with advanced solid tumors or lymphomas.^[17]

This article uses material from the Wikipedia article  Metasyntactic variable, which is released under the  Creative Commons Attribution-ShareAlike 3.0 Unported License.