{"entity":{"id":"tigit","kind":"target","name":"TIGIT","aka":[],"tldr":"TIGIT is an inhibitory receptor on T and natural killer cells that binds PVR (CD155) on tumour cells, so blocking it was expected to amplify PD-1 and PD-L1 inhibitors. Tiragolumab, domvanalimab and others then failed to add benefit in phase 3 lung cancer trials despite encouraging phase 2 signals, and the lack of a TIGIT-specific biomarker remains a weakness.","summary":"TIGIT is an inhibitory receptor on T and NK cells that binds PVR (CD155) on tumour cells and competes with the activating receptor CD226, so blocking it was expected to amplify PD-1 and PD-L1 inhibitors. That expectation largely failed in phase 3: tiragolumab (SKYSCRAPER-01), domvanalimab and others did not add meaningful benefit to PD-1/PD-L1 blockade in NSCLC or SCLC, despite encouraging phase 2 signals. Because TIGIT sits on immune cells, patient selection relied on PD-L1 rather than a TIGIT-specific biomarker, and this remains a weakness. Fc-enabled versus Fc-silent antibody design, which changes whether regulatory T cells are depleted, is still debated, and some programmes continue. The newcomer's lesson: TIGIT is a cautionary tale about promising early data that did not survive large randomised trials.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/TIGIT","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/TIGIT"}],"tags":["checkpoint","failed-so-far"],"related":[],"cancers":["nsclc","sclc"],"sections":[],"technologies":["tigit-blockade"],"targets":[],"drugs":["rilvegostomig","hb0036"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","t-cell-exhaustion"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"TIGIT","role":["immune-checkpoint"],"sources":[],"specificity":"immune-microenvironment","distribution":"one-type","specificityNote":"Immune or microenvironment target: the record's class is immune checkpoint. HPA TIGIT: RNA tissue enriched (lymphoid tissue 36 nTPM); blood lineage lineage enriched (T-cells 196 nTPM); no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Lung cancer (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 1 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas TIGIT tissue","url":"https://www.proteinatlas.org/ENSG00000181847-TIGIT/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt Q495A1","url":"https://www.uniprot.org/uniprotkb/Q495A1/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000181847 associations","url":"https://platform.opentargets.org/target/ENSG00000181847/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:26838","ensembl":"ENSG00000181847","uniprot":"Q495A1","entrez":"201633","firstDescribed":2004,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Ota et al, Nat. Genet, 2004, \"Complete sequencing and characterization of 21,243 full-length human cDNAs\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/14702039/","biology":"Binds PVR (CD155) on tumour cells; competes with the activating receptor CD226.","whereFound":["T and NK cells"],"targetClass":"checkpoint","prevalence":[{"cancerId":"nsclc","pct":"n/a","measure":"Immune-cell target; PD-L1 used for selection","source":"https://en.wikipedia.org/wiki/TIGIT"}]},"route":"/targets/tigit/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"tigit-blockade","kind":"technology","name":"TIGIT blockade","route":"/technologies/tigit-blockade/"}],"drug":[{"id":"hb0036","kind":"drug","name":"HB0036","route":"/drugs/hb0036/"},{"id":"rilvegostomig","kind":"drug","name":"Rilvegostomig","route":"/drugs/rilvegostomig/"},{"id":"tiragolumab","kind":"drug","name":"Tiragolumab","route":"/drugs/tiragolumab/"}],"pathway":[{"id":"nk-cell-recognition","kind":"pathway","name":"NK-cell recognition: missing self & stress ligands","route":"/pathways/nk-cell-recognition/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"t-cell-exhaustion","kind":"pathway","name":"T-cell exhaustion","route":"/pathways/t-cell-exhaustion/"}],"company":[{"id":"compugen","kind":"company","name":"Compugen","route":"/companies/compugen/"}],"pairing":[{"id":"tigit-plus-pd1-caution","kind":"pairing","name":"Caution: TIGIT + PD-(L)1 blockade","route":"/pairings/tigit-plus-pd1-caution/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"}],"target":[{"id":"nectin2","kind":"target","name":"CD112 (nectin-2)","route":"/targets/nectin2/"},{"id":"pvr","kind":"target","name":"CD155 (PVR)","route":"/targets/pvr/"},{"id":"cd96","kind":"target","name":"CD96","route":"/targets/cd96/"},{"id":"pvrig","kind":"target","name":"PVRIG (CD112R)","route":"/targets/pvrig/"},{"id":"tim3","kind":"target","name":"TIM-3","route":"/targets/tim3/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"},{"id":"immune-checkpoint","kind":"term","name":"Immune checkpoint","route":"/terms/immune-checkpoint/"}]}}