ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2021
Peripheral blood T-cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD-1 inhibitor.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 24 citations in OpenAlex.
- High peripheral T cell diversity is associated with lower risk of toxicity and superior response to dual immune checkpoint inhibitor therapy in patients with metastatic NSCLC.Journal for immunotherapy of cancer · 2024Trial
- First-line treatment of unresectable or metastatic HER2 positive esophagogastric adenocarcinoma: liquid biomarker analysis of the phase 2 INTEGA trial.Journal for immunotherapy of cancer · 2023Trial
- TCR sequencing in cancer immunology and immunotherapy: what, when, where, why, and how.Journal for immunotherapy of cancer · 2026Review
- ctDNA and immune biomarker testing for molecular residual disease surveillance and immune stratification in cancer.Frontiers in medicine · 2026Review
- Harnessing TCR repertoires: predictive insights and therapeutic monitoring in cancer immunotherapy.Immuno-oncology technology · 2025Review
- Exploring the potential of the TCR repertoire as a tumor biomarker (Review).Oncology letters · 2024Review
- DeepLION2: deep multi-instance contrastive learning framework enhancing the prediction of cancer-associated T cell receptors by attention strategy on motifs.Frontiers in immunology · 2024Article
- Clinical significance of peripheral T-cell receptor repertoire profiling and individualized nomograms in patients with gastrointestinal cancer treated with anti-programmed death 1 antibody.Translational gastroenterology and hepatology · 2024Article
- Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma.Frontiers in oncology · 2024Article
- Immune Diseases Associated with Aging: Molecular Mechanisms and Treatment Strategies.International journal of molecular sciences · 2023Review
- GENTLE: a novel bioinformatics tool for generating features and building classifiers from T cell repertoire cancer data.BMC bioinformatics · 2023Article
- Shaping the Future of Immunotherapy Targets and Biomarkers in Melanoma and Non-Melanoma Cutaneous Cancers.International journal of molecular sciences · 2023Review
- The potential role of the thymus in immunotherapies for acute myeloid leukemia.Frontiers in immunology · 2023Review
- Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy.Frontiers in immunology · 2021Review
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14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIdentifying valid biomarkers for patient selection impressively promotes the success of anti-PD-1 therapy. However, the unmet need for biomarkers in gastrointestinal (GI) cancers remains significant. We aimed to explore the predictive value of the circulating T-cell receptor (TCR) repertoire for clinical outcomes in GI cancers who received anti-PD-1 therapy.
methods137 pre- and 79 post-treated peripheral blood samples were included. The TCR repertoire was evaluated by sequencing of complementarity-determining region 3 (CDR3) in the TRB gene. The Shannon index was used to measure the diversity of the TCR repertoire, and Morisita's overlap index was used to determine TCR repertoire similarities between pre- and post-treated samples.
resultsAmong all enrolled patients, 76 received anti-PD-1 monotherapy and 61 received anti-PD-1 combination therapy. In the anti-PD-1 monotherapy cohort, patients with higher baseline TCR diversity exhibited a significantly higher disease control rate (77.8% vs. 47.2%; hazard ratio [HR] 3.92; 95% confidence interval [CI] 1.14-13.48; P = 0.030) and a longer progression-free survival (PFS) (median: 6.47 months vs. 2.77 months; HR 2.10; 95% CI 1.16-3.79; P = 0.014) and overall survival (OS) (median: NA vs. 8.97 months; HR 3.53; 95% CI 1.49-8.38; P = 0.004) than those with lower diversity. Moreover, patients with a higher TCR repertoire similarity still showed a superior PFS (4.43 months vs. 1.84 months; HR 13.98; 95% CI 4.37-44.68; P < 0.001) and OS (13.40 months vs. 6.12 months; HR 2.93; 95% CI 1.22-7.03; P = 0.016) even in the cohort with lower baseline diversity. However, neither biomarker showed predictive value in the anti-PD-1 combination therapy cohort. Interestingly, the combination of TCR diversity and PD-L1 expression can facilitate patient stratification in a pooled cohort.
conclusionThe circulating TCR repertoire can serve as a predictor of clinical outcomes in anti-PD-1 therapy in GI cancers.
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