ArticleESMO open2023
Circulating pre-treatment T-cell receptor repertoire as a predictive biomarker in advanced or metastatic non-small-cell lung cancer patients treated with pembrolizumab alone or in combination with chemotherapy.
Article in ESMO open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Guiding the Application of Immunotherapy in Nonsmall Cell Lung Cancer: The Role of Biomarkers.Thoracic cancer · 2026Review
- Toward uncertainty-aware clinical decision support for treatment response prediction in metastatic NSCLC: integrating FDG-PET, T-cell repertoire, and cytokines with conformal prediction.Research square · 2026Article
- Peripheral T-Cell Receptor β Repertoire Dynamics Correlate with Response to Anti-PD-L1 Therapy in Non-Small Cell Lung Cancer.Cancers · 2026Article
- Article
- Combination Immunotherapy as a Promising Strategy to Overcome Immunotherapy Resistance: From Emergence to Next-Generation Approaches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mechanism and intervention strategy of thymus atrophy in cancer immunotherapy.American journal of cancer research · 2026Review
- Stable global repertoire architecture masks short-term clonal remodeling in intratumoral TCR repertoires.Frontiers in immunology · 2026Article
- Harnessing TCR repertoires: predictive insights and therapeutic monitoring in cancer immunotherapy.Immuno-oncology technology · 2025Review
- Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients.Scientific reports · 2025Article
- [Research Progress on Immunosenescence in Elderly Patients with Advanced Non-small Cell Lung Cancer and Its Immunotherapy].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Napsin A-specific T-cell clonotypes are associated with improved clinical outcomes in patients receiving checkpoint immunotherapy for metastatic non-small cell lung cancer.Journal for immunotherapy of cancer · 2025Article
- Pre-treatment peripheral blood TCR repertoire as a predictor of response in patients with NSCLC treated with immunochemotherapy.BMC cancer · 2025Article
- New insights on potency assays from recent advances and discoveries in CAR T-cell therapy.Frontiers in immunology · 2025Review
- Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies.Blood cancer journal · 2024Review
- Exploring the potential of the TCR repertoire as a tumor biomarker (Review).Oncology letters · 2024Review
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8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe circulating T-cell receptor (TCR) repertoire is a dynamic representation of overall immune responses in an individual. MATERIALS AND
methodsWe prospectively collected baseline blood from patients treated with first-line pembrolizumab monotherapy or in combination with chemotherapy. TCR repertoire metrics were correlated with clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and immune-related adverse events (irAEs). We built a logistic regression classifier by fitting all four TCR-β repertoire metrics to the immune checkpoint inhibitor (ICI) CBR data. In the subsequent receiver operating characteristic (ROC) analysis of the resulting logistic regression model probabilities, the best cut-off value was selected to maximise sensitivity to predict CBR to ICI.
resultsWe observed an association between reduced number of unique clones and CBR among patients treated with pembrolizumab monotherapy (cohort 1) [risk ratio = 2.86, 95% confidence interval (CI) 1.04-8.73, P = 0.039]. For patients treated with pembrolizumab plus chemotherapy (cohort 2), increased number of unique clones [hazard ratio (HR) = 2.96, 95% CI 1.28-6.88, P = 0.012] and Shannon diversity (HR = 2.73, 95% CI 1.08-6.87, P = 0.033), and reduced evenness (HR = 0.43, 95% CI 0.21-0.90, P = 0.025) and convergence (HR = 0.41, 95% CI 0.19-0.90, P = 0.027) were associated with improved PFS, while only an increased number of unique clones (HR = 4.62, 95% CI 1.52-14.02, P = 0.007) were associated with improved OS. Logistic regression models combining the TCR repertoire metrics improved the prediction of CBR (cohorts 1 and 2) and were strongly associated with PFS (cohort 1, HR = 0.38, 95% CI 0.19-0.78, P = 0.009) and OS (cohort 2, HR = 0.20, 95% CI 0.05-0.76, P < 0.0001). Reduced TCR conversion was associated with increased frequency of irAEs needing systemic steroid treatment.
conclusionCombined pre-treatment circulating TCR metrics might serve as a predictive biomarker for clinical outcomes among patients with advanced non-small-cell lung cancer treated with pembrolizumab alone or in combination with chemotherapy.
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