{"entity":{"id":"idea-bio2-tcr-repertoire-early-readout","kind":"idea","name":"Watch the immune system's response in the blood three weeks in","aka":[],"tldr":"When immunotherapy works, specific immune cell families multiply in the blood within weeks. Tracking that could tell patients early whether to continue.","summary":"Peripheral T-cell receptor repertoire dynamics (clonal expansion, clonal replacement and the appearance of tumour-matched clones) have been associated with response in melanoma, lung and bladder cancer, but the analyses are retrospective, use different metrics and different platforms, and have never been locked as a prospective decision rule. Sequencing cost is now low enough for serial monitoring.","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":[],"cancers":["melanoma","nsclc","urothelial"],"sections":[],"technologies":["ngs-mrd-clonoseq","rna-seq","checkpoint-inhibitor","liquid-biopsy"],"targets":[],"drugs":[],"companies":["adaptive-biotechnologies"],"institutions":[],"pathways":[],"terms":["irae","orr"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A locked repertoire dynamics metric measured at baseline and three weeks identifies non-responders with negative predictive value above 85%, allowing early switch decisions before radiographic progression.","rationale":"Repertoire change is mechanistically upstream of tumour shrinkage, and blood is easy to sample serially. The same logic works clinically in leukaemia through clonality tracking, and the assays are already commercially available.","test":"Prospective locked-metric validation in an existing checkpoint inhibitor trial with serial blood samples, pre-registering the metric, threshold and analysis plan before unblinding.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":4},"route":"/ideas/idea-bio2-tcr-repertoire-early-readout/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","route":"/technologies/ngs-mrd-clonoseq/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"company":[{"id":"adaptive-biotechnologies","kind":"company","name":"Adaptive Biotechnologies","route":"/companies/adaptive-biotechnologies/"}],"term":[{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"}],"bottleneck":[{"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/"}]}}