Biology:VISTA (protein)
 Generic protein structure example |
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.[1][2][3]
Structure and function
VISTA is approximately 50kDa and belongs to the immunoglobulin superfamily and has one IgV domain.[4][1]
VISTA is part of the B7 family, is primarily expressed in white blood cells and its transcription is partially controlled by p53.[4][5] There is evidence that VISTA can act as both a ligand[6] and a receptor[7] on T cells to inhibit T cell effector function and maintain peripheral tolerance.[1][4]
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[8] and squamous cell carcinoma.[9]
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.[10]
As a drug target
There is an ongoing cancer immunotherapy clinical trial for a monoclonal antibody targeting VISTA in advanced cancer.[11] Preliminary results of the phase I clinical trial show good safety tolerance and anti-cancer activity in patients with advanced tumours.[12] 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.[13]
References
- ↑ 1.0 1.1 1.2 "Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators.". Frontiers in Immunology 6: 418. August 2015. doi:10.3389/fimmu.2015.00418. PMID 26347741.
- ↑ "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. Oct 2003. doi:10.1101/gr.1293003. PMID 12975309.
- ↑ "Entrez Gene: C10orf54 chromosome 10 open reading frame 54". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64115.
- ↑ 4.0 4.1 4.2 "Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53.". Science 349 (6247): 1966–75. July 31, 2015. doi:10.1126/science.1261669. PMID 26228159.
- ↑ "VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses.". Journal of Experimental Medicine 208 (3): 577–92. March 14, 2011. doi:10.1084/jem.20100619. PMID 21383057.
- ↑ "VISTA is an immune checkpoint molecule for human T cells.". Cancer Research 74 (7): 1924–32. April 1, 2014. doi:10.1158/0008-5472.CAN-13-1504. PMID 24691993.
- ↑ "Coinhibitory receptor PD-1H preferentially suppresses CD4⁺ T cell-mediated immunity.". Journal of Clinical Investigation 124 (5): 1966–75. April 17, 2014. doi:10.1172/JCI74589. PMID 24743150.
- ↑ "VISTA Regulates the Development of Protective Antitumor Immunity.". Cancer Research 74 (7): 1933–44. April 1, 2014. doi:10.1158/0008-5472.CAN-13-1506. PMID 24691994.
- ↑ "Differential contribution of three immune checkpoint (VISTA, CTLA-4, PD-1) pathways to antitumor responses against squamous cell carcinoma.". Oral Oncology 57: 54–60. May 3, 2016. doi:10.1016/j.oraloncology.2016.04.005. PMID 27208845.
- ↑ "Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals.". PLOS ONE 9 (10): e109103. October 3, 2014. doi:10.1371/journal.pone.0109103. PMID 25279955. Bibcode: 2014PLoSO...9j9103B.
- ↑ "A Study of Safety, Pharmacokinetics, Pharmacodynamics of JNJ-61610588 in Participants With Advanced Cancer". https://clinicaltrials.gov/ct2/show/NCT02671955.
- ↑ 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". https://clinicaltrials.gov/ct2/show/NCT02812875.
Further reading
- "Functional proteomics mapping of a human signaling pathway.". Genome Res. 14 (7): 1324–32. 2004. doi:10.1101/gr.2334104. PMID 15231748.
- "Signal peptide prediction based on analysis of experimentally verified cleavage sites.". Protein Sci. 13 (10): 2819–24. 2005. doi:10.1110/ps.04682504. PMID 15340161.
- "Large-scale cDNA transfection screening for genes related to cancer development and progression.". Proc. Natl. Acad. Sci. U.S.A. 101 (44): 15724–9. 2004. doi:10.1073/pnas.0404089101. PMID 15498874. Bibcode: 2004PNAS..10115724W.
- "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
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.
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