{"entity":{"id":"vista","kind":"target","name":"VISTA","aka":[],"tldr":"An immune checkpoint on myeloid cells that works at the acidic pH inside tumours and is a suspected escape route after PD-1 therapy; antibodies are in early trials.","summary":"VISTA (VSIR, PD-1H) is expressed mainly on myeloid cells and naive T cells, binds PSGL-1 selectively at acidic pH (tumour microenvironment) and VSIG3, and suppresses T-cell activation. It is upregulated after anti-CTLA-4 in prostate cancer and after chemotherapy in some tumours, suggesting adaptive resistance. Anti-VISTA antibodies (CI-8993, SNS-101 which binds only at low pH, HMBD-002, KVA12123) are in phase 1/2; the first agent (JNJ-61610588) was halted for cytokine release. No efficacy has yet been shown.","asOf":"2026-09-08","links":[{"label":"pH-selective VISTA (Nature 2019)","url":"https://doi.org/10.1038/s41586-019-1674-5"}],"tags":["gap-fill"],"related":["pd1","ctla4","tim3","lag3"],"cancers":["prostate","pancreatic","mesothelioma","nsclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-johnston-nature"],"journals":[],"dependsOn":[],"notes":["In prostate, pancreatic and lung cancer VISTA is carried mainly by myeloid infiltrates rather than tumour cells, so a tumour-cell prevalence is not well characterised."],"symbol":"VSIR","role":["immune-checkpoint"],"sources":[],"specificitySources":[],"hgnc":"HGNC:30085","ensembl":"ENSG00000107738","uniprot":"Q9H7M9","entrez":"64115","firstDescribed":2003,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Sachs U.J. et al, 2003, \"Gi24, a novel platelet receptor\".","firstDescribedSource":"https://www.uniprot.org/uniprotkb/Q9H7M9/entry","biology":"B7-family Ig-superfamily member acting as both ligand and receptor; histidine-rich extracellular domain makes PSGL-1 binding pH-dependent; expressed at high density on neutrophils, monocytes and MDSCs.","whereFound":["Myeloid infiltrates in prostate, pancreatic, lung, colorectal and ovarian cancers","Mesothelioma (tumour-cell expression)","AML blasts"],"targetClass":"checkpoint","prevalence":[{"cancerId":"mesothelioma","pct":85,"measure":"IHC, any VISTA on tumour cells (TMA, n=319; 88% epithelioid, 90% biphasic, 42% sarcomatoid)","source":"https://doi.org/10.1038/s41379-019-0364-z","note":"Expression on inflammatory cells in 94%; VISTA-high associated with better survival"}]},"route":"/targets/vista/","neighbours":{"target":[{"id":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"lag3","kind":"target","name":"LAG-3","route":"/targets/lag3/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"tim3","kind":"target","name":"TIM-3","route":"/targets/tim3/"}],"cancer":[{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"pathway":[{"id":"myeloid-suppression-axis","kind":"pathway","name":"Myeloid suppression: TAMs, MDSCs & don't-eat-me signals","route":"/pathways/myeloid-suppression-axis/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"paper":[{"id":"paper-johnston-nature","kind":"paper","name":"VISTA is an acidic pH-selective ligand for PSGL-1","route":"/key-papers/paper-johnston-nature/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"}]}}