{"entity":{"id":"lag3","kind":"target","name":"LAG-3","aka":[],"tldr":"LAG-3 is the third immune brake to reach approval, combined with PD-1 blockade in melanoma.","summary":"LAG-3 is an inhibitory receptor that binds MHC class II and FGL1 and is co-expressed with PD-1 on exhausted T cells, so blocking both releases two brakes on the same cell. Relatlimab plus nivolumab (Opdualag) improved progression-free survival over nivolumab alone in untreated advanced melanoma in RELATIVITY-047, with less toxicity than the ipilimumab combination, making LAG-3 the third immune checkpoint to reach approval. LAG-3 expression of at least 1 percent on immune cells was seen in roughly 75 to 80 percent of the RELATIVITY-047 population. Fianlimab and favezelimab are in phase 3 across tumour types, and whether the benefit extends beyond melanoma is the central open question. For a newcomer: LAG-3 is the immune brake that joined PD-1 blockade to make melanoma immunotherapy work better without much extra toxicity.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/LAG3","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/LAG3"}],"tags":["checkpoint"],"related":[],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["hlx26"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","t-cell-exhaustion"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"LAG3","role":["immune-checkpoint"],"sources":[],"specificity":"immune-microenvironment","distribution":"one-type","specificityNote":"Immune or microenvironment target: the record's class is immune checkpoint. HPA LAG3: RNA tissue enhanced (choroid plexus 13 nTPM, lymphoid tissue 22 nTPM, ovary 18 nTPM); blood lineage lineage enriched (T-cells 13 nTPM); no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Skin cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (melanoma). (Rule 1 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas LAG3 tissue","url":"https://www.proteinatlas.org/ENSG00000089692-LAG3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt P18627","url":"https://www.uniprot.org/uniprotkb/P18627/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000089692 associations","url":"https://platform.opentargets.org/target/ENSG00000089692/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:6476","ensembl":"ENSG00000089692","uniprot":"P18627","entrez":"3902","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Triebel et al, J. Exp. Med, 1990, \"LAG-3, a novel lymphocyte activation gene closely related to CD4\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1692078/","biology":"Binds MHC class II and FGL1; co-expressed with PD-1 on exhausted T cells.","whereFound":["Exhausted T cells"],"targetClass":"checkpoint","prevalence":[{"cancerId":"melanoma","pct":"75-80","measure":"LAG-3 >=1% on immune cells","source":"https://en.wikipedia.org/wiki/LAG3","note":"RELATIVITY-047 population"}]},"route":"/targets/lag3/","neighbours":{"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"drug":[{"id":"favezelimab","kind":"drug","name":"Favezelimab","route":"/drugs/favezelimab/"},{"id":"fianlimab","kind":"drug","name":"Fianlimab","route":"/drugs/fianlimab/"},{"id":"hlx26","kind":"drug","name":"HLX26","route":"/drugs/hlx26/"},{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/"}],"pathway":[{"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/"}],"trial":[{"id":"fianlimab-phase3-melanoma","kind":"trial","name":"Fianlimab + cemiplimab phase 3 (first-line melanoma)","route":"/trials/fianlimab-phase3-melanoma/"},{"id":"relativity-047","kind":"trial","name":"RELATIVITY-047","route":"/trials/relativity-047/"},{"id":"relativity-098","kind":"trial","name":"RELATIVITY-098","route":"/trials/relativity-098/"}],"pairing":[{"id":"lag3-adjuvant-caution","kind":"pairing","name":"Caution: LAG-3 blockade outside active disease","route":"/pairings/lag3-adjuvant-caution/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"lag3-blockade","kind":"technology","name":"LAG-3 blockade","route":"/technologies/lag3-blockade/"}],"person":[{"id":"hussein-tawbi","kind":"person","name":"Hussein A. Tawbi","route":"/people/hussein-tawbi/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"},{"id":"avoiding-immune-destruction","kind":"term","name":"Hallmark: avoiding immune destruction","route":"/terms/avoiding-immune-destruction/"},{"id":"immune-checkpoint","kind":"term","name":"Immune checkpoint","route":"/terms/immune-checkpoint/"},{"id":"t-cell","kind":"term","name":"T cell","route":"/terms/t-cell/"}],"target":[{"id":"fgl1","kind":"target","name":"FGL1","route":"/targets/fgl1/"},{"id":"tim3","kind":"target","name":"TIM-3","route":"/targets/tim3/"},{"id":"vista","kind":"target","name":"VISTA","route":"/targets/vista/"}],"paper":[{"id":"paper-checkmate-067-10-year-nejm-2025","kind":"paper","name":"CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma","route":"/key-papers/paper-checkmate-067-10-year-nejm-2025/"},{"id":"paper-pardoll-immune-checkpoint-blockade-nrc-2012","kind":"paper","name":"Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy","route":"/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/"},{"id":"paper-relativity-047-nejm-2022","kind":"paper","name":"RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma","route":"/key-papers/paper-relativity-047-nejm-2022/"}],"institution":[{"id":"pascale-naples","kind":"institution","name":"Istituto Nazionale Tumori IRCCS Fondazione G. Pascale","route":"/institutions/pascale-naples/"},{"id":"upmc-hillman","kind":"institution","name":"UPMC Hillman Cancer Center","route":"/institutions/upmc-hillman/"}],"company":[{"id":"immutep","kind":"company","name":"Immutep","route":"/companies/immutep/"}]}}