ArticleJournal for immunotherapy of cancer2023
T-cell receptor beta variable gene polymorphism predicts immune-related adverse events during checkpoint blockade immunotherapy.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- The Immune Checkpoint Inhibitors Journey: From Early Promise to Lasting Impact.Journal of immunotherapy and precision oncology · 2026Review
- Unmasking human T cell receptor germline diversity: 335 novel alleles identified in 47 Pangenome reference individuals using the gAIRR Suite.Journal of advanced research · 2026Article
- A multi-ethnic reference map of T cell receptor germline diversity reveals evidence of natural selection on alpha chain genes.Nature communications · 2026Article
- Toward nursing-integrated biomarker surveillance for immune-related adverse events during immune checkpoint inhibitor therapy.Frontiers in medicine · 2026Review
- The role of metabolites in the causal effect of immune cell phenotypes on immunotherapy toxicity risk.Discover oncology · 2025Article
- ALIGaToR: A tool for the automated annotation of immunoglobulin and T cell receptor genomic loci.bioRxiv : the preprint server for biology · 2025Article
- Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies.Frontiers in immunology · 2025Review
- ALIGaToR: a tool for the automated annotation of immunoglobulin and T cell receptor genomic loci.Oxford open immunology · 2025Article
- The Roles of T cells in Immune Checkpoint Inhibitor-Induced Arthritis.Aging and disease · 2024Review
- Reconstitution of peripheral blood T cell receptor β immune repertoire in immune checkpoint inhibitors associated myocarditis.Cardio-oncology (London, England) · 2024Article
- Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors.Cancers · 2024Review
- Digger: directed annotation of immunoglobulin and T cell receptor V, D, and J gene sequences and assemblies.Bioinformatics (Oxford, England) · 2024Article
- Pulmonary toxicity of immune checkpoint immunotherapy.The Journal of clinical investigation · 2024Review
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundImmune checkpoint inhibitors have revolutionized cancer treatment. However, they are associated with a unique spectrum of side effects, called immune-related adverse events (irAEs), which can cause significant morbidity and quickly progress to severe or life-threatening events if not treated promptly. Identifying predictive biomarkers for irAEs before immunotherapy initiation is therefore a critical area of research. Polymorphisms within the T-cell receptor beta (TCRB) variable (TRBV) gene have been implicated in autoimmune disease and may be mechanistically linked to irAEs. However, the repetitive nature of the TCRB locus and incomplete genome assembly has hampered the evaluation of TRBV polymorphisms in the past. PATIENTS AND
methodsWe used a novel method for long-amplicon next generation sequencing of rearranged TCRB chains from peripheral blood total RNA to evaluate the link between TRBV polymorphisms and irAEs in patients treated with immunotherapy for cancer. We employed multiplex PCR to create amplicons spanning the three beta chain complementarity-determining regions (CDR) regions to enable detection of polymorphism within the germline-encoded framework and CDR1 and CDR2 regions in addition to CDR3 profiling. Resultant amplicons were sequenced via the Ion Torrent and TRBV allele profiles constructed for each individual was correlated with irAE annotations to identify haplotypes associated with severe irAEs (≥ grade 3).
resultsOur study included 81 patients who had irAEs when treated with immunotherapy for cancer. By using principal component analysis of the 81 TRBV allele profiles followed by k-means clustering, we identified six major TRBV haplotypes. Strikingly, we found that one-third of this cohort possessed a TRBV allele haplotype that appeared to be protective against severe irAEs.
conclusionThe data suggest that long-amplicon TCRB repertoire sequencing can potentially identify TRBV haplotype groups that correlate with the risk of severe irAEs. Germline-encoded TRBV polymorphisms may serve as a predictive biomarker of severe irAEs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.