ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Cetuximab Responses in Patients with HNSCC Correlate to Clonal Expansion Feature of Peripheral and Tumor-Infiltrating T Cells with Top T-Cell Receptor Clonotypes.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 17 citations in OpenAlex.
- Stereotactic Body Radiation Therapy With Pembrolizumab in Programmed Cell Death Protein 1 Inhibitor-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Phase 2 Trial.International journal of radiation oncology, biology, physics · 2026Trial
- Long-term Survival and Molecular Biomarker Evaluation of a Phase II Cetuximab and Nivolumab Clinical Trial in Recurrent/Metastatic Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Neoadjuvant tislelizumab with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-1): a phase 2 clinical trial.Nature communications · 2025Trial
- Biomarkers Predictive of Immunotherapy Efficacy in Head and Neck Squamous Cell Carcinoma: Current Insights and Future Perspectives.World journal of otorhinolaryngology - head and neck surgery · 2026Review
- Immune-metabolic profiling of triple-negative breast cancer during neoadjuvant chemotherapy.iScience · 2026Article
- Preexisting TCR Clones Drive Major Pathologic Responses in Patients with HNSCC Treated with Dual Immune Checkpoint Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- TCRdb 2.0: an updated T-cell receptor sequence database.Nucleic acids research · 2026Article
- Stable global repertoire architecture masks short-term clonal remodeling in intratumoral TCR repertoires.Frontiers in immunology · 2026Article
- Lentiviral-mediated panErbB CAR-T cell therapy against head and neck squamous cell carcinomas for patients with Fanconi anemia.Molecular therapy. Oncology · 2025Article
- Multi-omics analysis reveals the role of tumor-infiltrating CD4BMC cancer · 2025Article
- Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.Molecular cancer · 2025Review
- Tumor-infiltrating nociceptor neurons promote immunosuppression.Science signaling · 2025Article
- Article
- T-cell Receptor Repertoire Analysis in the Context of Transarterial Chemoembolization Synergy with Systemic Therapy for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2025Review
- Exploring the potential of the TCR repertoire as a tumor biomarker (Review).Oncology letters · 2024Review
- Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review).Oncology reports · 2024Review
- FRZB: a potential prognostic marker for head and neck squamous cell carcinoma.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Differential tumor immune microenvironment coupled with tumor progression or tumor eradication in HPV-antigen expressing squamous cell carcinoma (SCC) models.Frontiers in immunology · 2024Article
- Perspectives in Immunotherapy: meeting report from Immunotherapy Bridge (Naples, November 30th-December 1st, 2022).Journal of translational medicine · 2023Article
- Host-specific differences in top-expanded TCR clonotypes correlate with divergent outcomes of anti-PD-L1 treatment in responders versus non-responders.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCetuximab is a standard-of-care treatment for head and neck squamous cell carcinoma (HNSCC). Well-defined correlative markers of therapeutic responses are still lacking. Characterizing dynamic changes of T-cell receptor (TCR) repertoire in peripheral blood and tumor tissue may facilitate developing markers for cetuximab response in HNSCCs. EXPERIMENTAL
designWe analyzed high-throughput TCRβ sequencing data generated with ImmunoSEQ platform using peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) from patients with HNSCC before and after cetuximab treatment (pre-/post-PBMC vs. pre-/post-TIL). Multiple analytic approaches were employed to normalize sequencing data.
resultsNormalized TCR richness was significantly lower in post-TIL than pre-TIL, suggesting that cetuximab reduced TCR diversity and promoted TCR expansion in TIL samples, regardless of response status. The magnitude of clonal expansion (defined as expansion rate) in top 20 TCR clonotypes was significantly higher in responder PBMC with or without normalization, and in responder TIL upon normalization, than nonresponder ones. Notably, the expanded top 20 or top 50 TCR clonotypes overlapped between PBMC and TIL samples, which occurred significantly more frequently in responders than nonresponders.
conclusionsPatients with cetuximab-treated HNSCC harbor dynamic changes of TCR repertoires correlative to therapeutic responses. The expansion rate of top TCR clonotypes in peripheral blood may serve as a minimally invasive, readily accessible, and feasible marker for predicting cetuximab responses in HNSCCs and beyond, and the expansion rate of top TCR clonotypes in TILs and their overlapping probability between PBMC and TIL may serve as additional predictive markers. Our study also highlights the importance of data normalization for TCR repertoire analysis.
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Registered trials
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.