{"doi":"10.1136/jitc-2021-002642","title":"Evaluating T-cell cross-reactivity between tumors and immune-related adverse events with TCR sequencing: pitfalls in interpretations of functional relevance","abstract":"T-cell receptor sequencing (TCRseq) enables tracking of T-cell clonotypes recognizing the same antigen over time and across biological compartments. TCRseq has been used to test if cross-reactive antitumor T cells are responsible for development of immune-related adverse events (irAEs) following immune checkpoint blockade. Prior studies have interpreted T-cell clones shared among the tumor and irAE as evidence supporting this, but interpretations of these findings are challenging, given the constraints of TCRseq. Here we capitalize on a rare opportunity to understand the impact of potential confounders, such as sample size, tissue compartment, and collection batch/timepoint, on the relative proportion of shared T-cell clones between an irAE and tumor specimens. TCRseq was performed on tumor-involved and -uninvolved tissues, including an irAE, that were obtained throughout disease progression and at the time of rapid autopsy from a patient with renal cell carcinoma treated with programmed death-1 (PD-1) blockade. Our analyses show significant effects of these confounders on our ability to understand T-cell receptor overlap, and we present mitigation strategies and study design recommendations to reduce these errors. Implementation of these strategies will enable more rigorous TCRseq-based studies of immune responses in human tissues, particularly as they relate to antitumor T-cell cross-reactivity in irAEs following checkpoint blockade.","journal":"Journal for ImmunoTherapy of Cancer","year":2021,"id":178557,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":490805,"name":"Jiajia Zhang","orcid":"0000-0003-4623-6134","position":1,"is_corresponding":false},{"id":615677,"name":"Boyang Zhang","orcid":"0000-0002-4702-7628","position":2,"is_corresponding":false},{"id":724392,"name":"Genevieve J. Kaunitz","orcid":"0000-0001-9619-0109","position":3,"is_corresponding":false},{"id":617043,"name":"Poromendro Burman","orcid":null,"position":4,"is_corresponding":false},{"id":725122,"name":"Hok-Yee Chan","orcid":null,"position":5,"is_corresponding":false},{"id":254621,"name":"Franco Verde","orcid":"0000-0002-9659-2594","position":6,"is_corresponding":false},{"id":278995,"name":"Jody E. Hooper","orcid":"0000-0002-8209-3559","position":7,"is_corresponding":false},{"id":232505,"name":"Hans J. Hammers","orcid":"0000-0002-6224-4559","position":8,"is_corresponding":false},{"id":272254,"name":"Mohamad E. Allaf","orcid":"0000-0003-3333-3904","position":9,"is_corresponding":false},{"id":233094,"name":"Hongkai Ji","orcid":"0000-0002-6480-0141","position":10,"is_corresponding":false},{"id":59435,"name":"Janis M. Taube","orcid":"0000-0002-8273-4395","position":11,"is_corresponding":false},{"id":62880,"name":"Kellie N. Smith","orcid":"0000-0002-6295-8930","position":12,"is_corresponding":false},{"id":254620,"name":"Tricia R. Cottrell","orcid":"0000-0003-2952-1830","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:40.592580Z","pmid":"34230111","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}