From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
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, Dies1External IDs
OMIM :
615608 ;
MGI :
1921298 ;
HomoloGene :
81923 ;
GeneCards :
VSIR ;
OMA :
VSIR - orthologs
Wikidata
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 VSIR
gene .
[5]
[6]
[7]
Structure and function
VISTA is approximately 50
kDa 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 significance
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 target
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]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000107738 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000020101 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
a
b
c Le Mercier I, Lines JL, Noelle RJ (August 2015).
"Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators" . Frontiers in Immunology . 6 : 418.
doi :
10.3389/fimmu.2015.00418 .
PMC
4544156 .
PMID
26347741 .
^ Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A (Oct 2003).
"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment" . Genome Res . 13 (10): 2265–70.
doi :
10.1101/gr.1293003 .
PMC
403697 .
PMID
12975309 .
^
"Entrez Gene: C10orf54 chromosome 10 open reading frame 54" .
^
a
b
c Yoon KW, Byun S, Kwon E, Hwang SY, Chu K, Hiraki M, Jo SH, Weins A, Hakroush S, Cebulla A, Sykes DB, Greka A, Mundel P, Fisher DE, Mandinova A, Lee SW (July 31, 2015).
"Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53" . Science . 349 (6247): 1966–75.
doi :
10.1126/science.1261669 .
PMC
5215039 .
PMID
26228159 .
^ Wang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, Lu LF, Gondek D, Wang Y, Fava RA, Fiser A, Almo S, Noelle RJ (March 14, 2011).
"VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses" . Journal of Experimental Medicine . 208 (3): 577–92.
doi :
10.1084/jem.20100619 .
PMC
3058578 .
PMID
21383057 .
^ Lines JL, Pantazi E, Mak J, Sempere LF, Wang L, O'Connell S, Ceeraz S, Suriawinata AA, Yan S, Ernstoff MS, Noelle R (April 1, 2014).
"VISTA is an immune checkpoint molecule for human T cells" . Cancer Research . 74 (7): 1924–32.
doi :
10.1158/0008-5472.CAN-13-1504 .
PMC
3979527 .
PMID
24691993 .
^ Flies DB, Han X, Higuchi T, Zheng L, Sun J, Ye JJ, Chen L (April 17, 2014).
"Coinhibitory receptor PD-1H preferentially suppresses CD4⁺ T cell-mediated immunity" . Journal of Clinical Investigation . 124 (5): 1966–75.
doi :
10.1172/JCI74589 .
PMC
4001557 .
PMID
24743150 .
^ Le Mercier I, Chen W, Lines JL, Day M, Li J, Sergent P, Noelle RJ, Wang L (April 1, 2014).
"VISTA Regulates the Development of Protective Antitumor Immunity" . Cancer Research . 74 (7): 1933–44.
doi :
10.1158/0008-5472.CAN-13-1506 .
PMC
4116689 .
PMID
24691994 .
^ Kondo Y, Ohno T, Nishii N, Harada K, Yagita H, Azuma M (May 3, 2016). "Differential contribution of three immune checkpoint (VISTA, CTLA-4, PD-1) pathways to antitumor responses against squamous cell carcinoma". Oral Oncology . 57 : 54–60.
doi :
10.1016/j.oraloncology.2016.04.005 .
PMID
27208845 .
^ Bharaj P, Chahar HS, Alozie OK, Rodarte L, Bansal A, Goepfert PA, Dwivedi A, Manjunath N, Shankar P (October 3, 2014).
"Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals" . PLOS ONE . 9 (10): e109103.
Bibcode :
2014PLoSO...9j9103B .
doi :
10.1371/journal.pone.0109103 .
PMC
4184823 .
PMID
25279955 .
^
"A Study of Safety, Pharmacokinetics, Pharmacodynamics of JNJ-61610588 in Participants With Advanced Cancer" . Retrieved September 25, 2016 .
^ Calvo, Emiliano (February 26, 2018). "Interim results of a phase 1/2 study of JNJ-63723283, an anti-PD-1 monoclonal antibody, in patients with advanced cancers". Journal of Clinical Oncology . 36 (5_suppl): 58.
doi :
10.1200/JCO.2018.36.5_suppl.58 .
^
"A Study of CA-170 (Oral PD-L1, PD-L2 and VISTA Checkpoint Antagonist) in Patients With Advanced Tumors and Lymphomas" . Retrieved September 26, 2016 .
Further reading
Colland F, Jacq X, Trouplin V, et al. (2004).
"Functional proteomics mapping of a human signaling pathway" . Genome Res . 14 (7): 1324–32.
doi :
10.1101/gr.2334104 .
PMC
442148 .
PMID
15231748 .
Zhang Z, Henzel WJ (2005).
"Signal peptide prediction based on analysis of experimentally verified cleavage sites" . Protein Sci . 13 (10): 2819–24.
doi :
10.1110/ps.04682504 .
PMC
2286551 .
PMID
15340161 .
Wan D, Gong Y, Qin W, et al. (2004).
"Large-scale cDNA transfection screening for genes related to cancer development and progression" . Proc. Natl. Acad. Sci. U.S.A . 101 (44): 15724–9.
Bibcode :
2004PNAS..10115724W .
doi :
10.1073/pnas.0404089101 .
PMC
524842 .
PMID
15498874 .
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . 437 (7062): 1173–8.
Bibcode :
2005Natur.437.1173R .
doi :
10.1038/nature04209 .
PMID
16189514 .
S2CID
4427026 .
External links
Overview of all the structural information available in the
PDB for
UniProt :
Q9H7M9 (V-type immunoglobulin domain-containing suppressor of T-cell activation) at the
PDBe-KB .