ArticleJournal for immunotherapy of cancer2023
T-cell tolerant fraction as a predictor of immune-related adverse events.
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 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Blood parameters and whole-blood transcriptomics associated with immune-related adverse events in metastatic renal cell carcinoma during nivolumab plus ipilimumab.Scientific reports · 2026Article
- Association of PD-L1 expression with systemic immune parameters in non-small cell lung cancer.Translational lung cancer research · 2025Article
- Innate and adaptive immune features associated with immune-related adverse events.Journal for immunotherapy of cancer · 2025Article
- Molecular analysis of immune checkpoint inhibitor associated erythema nodosum-like toxicity.Frontiers in immunology · 2025Article
- The Current and Future of Biomarkers of Immune Related Adverse Events.Rheumatic diseases clinics of North America · 2024Review
- Highly variable timing renders immunotherapy efficacy and toxicity impractical biomarkers of one another in clinical practice.Frontiers in immunology · 2024Article
- Checkpoint Inhibitor-Associated Diabetes Mellitus Following Rapid Pancreatic Metastasis Resolution: Implications for Endocrine Toxicities in Immunotherapy.AACE endocrinology and diabetesArticle
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundImmune checkpoint inhibitor (ICI) therapies may cause unpredictable and potentially severe autoimmune toxicities termed immune-related adverse events (irAEs). Because T cells mediate ICI effects, T cell profiling may provide insight into the risk of irAEs. Here we evaluate a novel metric-the T-cell tolerant fraction-as a predictor of future irAEs.
methodsWe examined T-cell receptor beta (TRB) locus sequencing from baseline pretreatment samples from an institutional registry and previously published studies. For each patient, we used TRB sequences to calculate the T-cell tolerant fraction, which was then assessed as a predictor of future irAEs (classified as Common Terminology Criteria for Adverse Event grade 0-1 vs grade ≥2). We then compared the tolerant fraction to TRB clonality and diversity. Finally, the tolerant fraction was assessed on (1) T cells enriched against napsin A, a potential autoantigen of irAEs; (2) thymic versus peripheral blood T cells; and (3) TRBs specific for various infections and autoimmune diseases.
resultsA total of 77 patients with cancer (22 from an institutional registry and 55 from published studies) receiving ICI therapy (43 CTLA4, 19 PD1/PDL1, 15 combination CTLA4+PD1/PDL1) were included in the study. The tolerant fraction was significantly lower in cases with clinically significant irAEs (p<0.001) and had an area under the receiver operating curve (AUC) of 0.79. The tolerant fraction was lower for each ICI treatment category, reaching statistical significance for CTLA4 (p<0.001) and demonstrating non-significant trends for PD1/PDL1 (p=0.21) and combination ICI (p=0.18). The tolerant fraction for T cells enriched against napsin A was lower than other samples. The tolerant fraction was also lower in thymic versus peripheral blood samples, and lower in some (multiple sclerosis) but not other (type 1 diabetes) autoimmune diseases. In our study cohort, TRB clonality had an AUC of 0.62, and TRB diversity had an AUC of 0.60 for predicting irAEs.
conclusionsAmong patients receiving ICI, the baseline T-cell tolerant fraction may serve as a predictor of clinically significant irAEs.
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