{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Barnet MB"],"funding":["Bioplatforms Australia (Bioplatforms)","Bill and Patricia Ritchie Foundation","NHMRC","Kinghorn Foundation (The Kinghorn Foundation)"],"pagination":["e2314258122"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12280981"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(28)"],"pubmed_abstract":["Lung cancers and melanomas have many somatically mutated self-proteins that would be expected to trigger an immune rejection response, yet therapeutic responses can only be induced in a subset of patients. Here, we investigated the possibility that inherited differences in immune tolerance checkpoints contribute to variability in outcomes. Whole genome sequencing revealed biallelic germline loss-of-function (LOF) mutations in the immune tolerance checkpoint gene, <i>NOD2</i>, in an exceptional immune responder to targeted radiotherapy for metastatic melanoma. In 40 exceptional immune responders to anti-PD1 monotherapy for non-small cell lung cancer (NSCLC), genome sequencing showed 30% had inherited a <i>NOD2</i> LOF variant, more than twice the population frequency (<i>P</i> = 0.0021). Co"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Common inherited loss-of-function mutations in the innate sensor NOD2 contribute to exceptional immune response to cancer immunotherapy."],"pmcid":["PMC12280981"],"funding_grant_id":["no grant number","APP2010134"],"pubmed_authors":["Mawson A","Zhang F","Gao B","Peters G","Wright K","Khan Z","Jara CJ","Burnett DL","Hold GL","John T","Peters TJ","Cooper WA","Kao SC","Bruce J","Masle-Farquhar E","Jackson KJL","Boyer M","Davis ID","Barnet MB","Cebon J","Faulks M","Pugh T","Russell A","Hui R","Goodnow CC","Heller G","Behren A","Joshua AM","Yang C","Blinman PL","Allen I","Chye A","Brink R","Junankar S","Nagrial A","Prokopec S"],"additional_accession":[]},"is_claimable":false,"name":"Common inherited loss-of-function mutations in the innate sensor NOD2 contribute to exceptional immune response to cancer immunotherapy.","description":"Lung cancers and melanomas have many somatically mutated self-proteins that would be expected to trigger an immune rejection response, yet therapeutic responses can only be induced in a subset of patients. Here, we investigated the possibility that inherited differences in immune tolerance checkpoints contribute to variability in outcomes. Whole genome sequencing revealed biallelic germline loss-of-function (LOF) mutations in the immune tolerance checkpoint gene, <i>NOD2</i>, in an exceptional immune responder to targeted radiotherapy for metastatic melanoma. In 40 exceptional immune responders to anti-PD1 monotherapy for non-small cell lung cancer (NSCLC), genome sequencing showed 30% had inherited a <i>NOD2</i> LOF variant, more than twice the population frequency (<i>P</i> = 0.0021). Co","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-03-27T15:26:00.539Z","creation":"2025-08-23T03:09:29.057Z"},"accession":"S-EPMC12280981","cross_references":{"pubmed":["40623177"],"doi":["10.1073/pnas.2314258122"]}}