ArticleCancer research2015
CTLA-4⁺ Regulatory T Cells Increased in Cetuximab-Treated Head and Neck Cancer Patients Suppress NK Cell Cytotoxicity and Correlate with Poor Prognosis.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
174 citing papers in PubMed, 1 synthesis or guideline pooled it, 260 citations in OpenAlex.
- Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised.Frontiers in medicine · 2020Pooled it
- 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
- Tumor immune microenvironment alterations using induction cetuximab in a phase II trial of deintensified therapy for p16-positive oropharynx cancer.Head & neck · 2023Trial
- Phase II Multi-institutional Clinical Trial Result of Concurrent Cetuximab and Nivolumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Neoadjuvant nivolumab for patients with resectable HPV-positive and HPV-negative squamous cell carcinomas of the head and neck in the CheckMate 358 trial.Journal for immunotherapy of cancer · 2021Trial
- Nivolumab in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: Efficacy and Safety in CheckMate 141 by Prior Cetuximab Use.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- A Phase I/II Trial of Cetuximab in Combination with Interleukin-12 Administered to Patients with Unresectable Primary or Recurrent Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- PD-L1 Mediates Dysfunction in Activated PD-1Cancer immunology research · 2018Trial
- EGFR signaling suppresses type 1 cytokine-induced T-cell attracting chemokine secretion in head and neck cancer.PloS one · 2018Trial
- Increased PD-1Cancer immunology research · 2017Trial
- The KRAS-Variant and Cetuximab Response in Head and Neck Squamous Cell Cancer: A Secondary Analysis of a Randomized Clinical Trial.JAMA oncology · 2017Trial
- Cetuximab activity in dysplastic lesions of the upper aerodigestive tract.Oral oncology · 2016Trial
- Natural killer cells in ovarian cancer therapy: mechanisms, evasion, and therapeutic innovations.Inflammopharmacology · 2026Review
- Small extracellular vesicles from the plasma of head and neck cancer patients induce dysfunctional T cell phenotypes.British journal of cancer · 2026Article
- Uncovering the Potential of 3D Spheroids for Modeling the Cellular Crosstalk Within the Tumor Microenvironment in HNSCC.Biotechnology journal · 2026Review
- A lactate-α-ketoglutarate metabolic circuit in tumor-infiltrating regulatory T cells accelerates tumor progression by inducing NK cell senescence.Nature cancer · 2026Article
- Targeting the NKG2D axis in head and neck squamous cell carcinoma: from molecular insights to clinical applications.Cancer cell international · 2026Review
- FcγR-driven chimeric receptor T cells in cancer therapy: a novel frontier in antibody-guided immunotherapy.Cancer cell international · 2026Review
- Characterizing the Head and Neck Cancer Microenvironment: Implications for Immunotherapy and Prognosis.Advances in experimental medicine and biology · 2026Review
- Harnessing the Power of CAR-NK Cells for Solid Tumors: Challenges, Innovations, and Future Frontiers in Immunotherapy.Cancer communications (London, England) · 2026Review
114 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The EGFR-targeted antibody cetuximab is effective against head and neck cancer (HNSCC), but in only 15% to 20% of patients, and the variability and extent of cetuximab-mediated cellular immunity is not fully understood. We hypothesized that regulatory T cells (Treg) may exert a functional and clinical impact on antitumor immunity in cetuximab-treated individuals. The frequency, immunosuppressive phenotype, and activation status of Treg and natural killer (NK) cells were analyzed in the circulation and tumor microenvironment of cetuximab-treated patients with HNSCC enrolled in a novel neoadjuvant, single-agent cetuximab clinical trial. Notably, cetuximab treatment increased the frequency of CD4(+)FOXP3(+) intratumoral Treg expressing CTLA-4, CD39, and TGFβ. These Treg suppressed cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) and their presence correlated with poor clinical outcome in two prospective clinical trial cohorts. Cetuximab expanded CTLA-4(+)FOXP3(+) Treg in vitro, in part, by inducing dendritic cell maturation, in combination with TGFβ and T-cell receptor triggering. Importantly, cetuximab-activated NK cells selectively eliminated intratumoral Treg but preserved effector T cells. In ex vivo assays, ipilimumab targeted CTLA-4(+) Treg and restored cytolytic functions of NK cells mediating ADCC. Taken together, our results argue that differences in Treg-mediated suppression contribute to the clinical response to cetuximab treatment, suggesting its improvement by adding ipilimumab or other strategies of Treg ablation to promote antitumor immunity.
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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.