{"entity":{"id":"idea-bio2-antigen-presentation-triage","kind":"idea","name":"Check whether a tumour can still show itself to the immune system","aka":[],"tldr":"Some tumours have broken the machinery that displays their identity to immune cells. Those patients cannot benefit from most immunotherapy and should be routed elsewhere.","summary":"Loss of HLA heterozygosity, B2M mutation, JAK1/2 loss and antigen presentation machinery defects are recurrent mechanisms of primary and acquired checkpoint resistance, and each is detectable from sequencing of tumour and germline. Routine reporting of an antigen presentation integrity score would identify patients who should be routed to HLA-independent therapies such as antibody-drug conjugates, natural killer cell engagers or CAR products.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":["oncokb","genie"],"cancers":[],"sections":[],"technologies":["wes-wgs","cgp","checkpoint-inhibitor","t-cell-engager","adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hla-a02-restriction","neoantigen","resistance"],"trials":[],"people":["charles-swanton","ton-schumacher"],"bottlenecks":["b-immunotherapy-response","b-resistance","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients with antigen presentation defects derive little or no benefit from checkpoint blockade, and prospectively routing them to HLA-independent therapy improves survival compared with standard checkpoint therapy.","rationale":"The mechanism is causally necessary for T-cell recognition, so the prediction is mechanistic rather than correlative. HLA loss of heterozygosity calling from standard sequencing data is already available in research pipelines and could be added to commercial reports at low cost.","test":"Add antigen presentation integrity calling to an existing sequencing pipeline, test the interaction with checkpoint benefit retrospectively in trial cohorts, then run a strategy trial in defect-positive patients.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":5},"route":"/ideas/idea-bio2-antigen-presentation-triage/","neighbours":{"collection":[{"id":"genie","kind":"collection","name":"AACR Project GENIE","route":"/collections/genie/"},{"id":"oncokb","kind":"collection","name":"OncoKB","route":"/collections/oncokb/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"hla-a02-restriction","kind":"term","name":"HLA-A*02:01 restriction","route":"/terms/hla-a02-restriction/"},{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"}],"person":[{"id":"charles-swanton","kind":"person","name":"Charles Swanton","route":"/people/charles-swanton/"},{"id":"ton-schumacher","kind":"person","name":"Ton Schumacher","route":"/people/ton-schumacher/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}]}}