ArticleCancer immunology research2015
STAT1-Induced HLA Class I Upregulation Enhances Immunogenicity and Clinical Response to Anti-EGFR mAb Cetuximab Therapy in HNC Patients.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group.Annals of oncology : official journal of the European Society for Medical Oncology · 2020Pooled it
- EGFR signaling suppresses type 1 cytokine-induced T-cell attracting chemokine secretion in head and neck cancer.PloS one · 2018Trial
- Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2016Trial
- Deciphering KRAS inhibitor resistance.Nature cell biology · 2026Article
- Extracellular vesicles from cytokine-treated human pancreatic ductal cells enhance HLA class I expression in beta cells.Frontiers in immunology · 2026Article
- Antigen processing machinery deficits in head and neck cancers: mechanisms of immune evasion and strategies for therapeutic restoration.Frontiers in oncology · 2026Review
- MarkerPredict: predicting clinically relevant predictive biomarkers with machine learning.NPJ systems biology and applications · 2025Article
- Therapeutic stress triggers tumor STAT1 acetylation to disarm immunotherapy.Cell reports. Medicine · 2025Article
- EP300 compromises antitumor immunity by increasing SOCS1 expression.Journal for immunotherapy of cancer · 2025Article
- Molecular Adaptations to Repeated Radiation Exposure in Triple-Negative Breast Cancer: Dysregulation of Cell Adhesion, Mitochondrial Function, and Epithelial-Mesenchymal Transition.International journal of molecular sciences · 2025Article
- Immune Modulation Through KIR-HLA Interactions Influences Cetuximab Efficacy in Colorectal Cancer.International journal of molecular sciences · 2025Article
- IL-4 mediated TAP2 downregulation is a dominant and reversible mechanism of immune evasion and immunotherapy resistance in non-small cell lung cancer.Molecular cancer · 2025Article
- Targeting EGFR-binding protein SLC7A11 enhancing antitumor immunity of T cells via inducing MHC-I antigen presentation in nasopharyngeal carcinoma.Cell death & disease · 2025Article
- Immune escape of head and neck cancer mediated by the impaired MHC-I antigen presentation pathway.Oncogene · 2024Review
- Phase Ib study of anti-EGFR antibody (SCT200) in combination with anti-PD-1 antibody (SCT-I10A) for patients with RAS/BRAF wild-type metastatic colorectal cancer.Cancer biology & medicine · 2023Article
- Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects.Molecular cancer · 2023Review
- Article
- Major histocompatibility complex class I molecule expression by pancreatic cancer cells is regulated by activation and inhibition of the epidermal growth factor receptor.Immunologic research · 2022Article
- Temporal regulation of interferon signalling in human EndoC-βH1 cells.Journal of molecular endocrinology · 2022Article
- Human Leukocyte Antigen Class I Antigen-Processing Machinery Upregulation by Anticancer Therapies in the Era of Checkpoint Inhibitors: A Review.JAMA oncology · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The goal of this study was to characterize the molecular mechanisms underlying cetuximab-mediated upregulation of HLA class I antigen-processing machinery components in head and neck cancer (HNC) cells and to determine the clinical significance of these changes in cetuximab-treated HNC patients. Flow cytometry, signaling studies, and chromatin immunoprecipitation (ChIP) assays were performed using HNC cells treated with cetuximab alone or with Fcγ receptor (FcγR)-bearing lymphocytes to establish the mechanism of EGFR-dependent regulation of HLA APM expression. A prospective phase II clinical trial of neoadjuvant cetuximab was used to correlate HLA class I expression with clinical response in HNC patients. EGFR blockade triggered STAT1 activation and HLA upregulation, in a src homology-containing protein (SHP)-2-dependent fashion, more prominently in HLA-B/C than in HLA-A alleles. EGFR signaling blockade also enhanced IFNγ receptor 1 (IFNAR) expression, augmenting induction of HLA class I and TAP1/2 expression by IFNγ, which was abrogated in STAT1(-/-) cells. Cetuximab enhanced HNC cell recognition by EGFR853-861-specific CTLs, and notably enhanced surface presentation of a non-EGFR peptide (MAGE-3271-279). HLA class I upregulation was significantly associated with clinical response in cetuximab-treated HNC patients. EGFR induces HLA downregulation through SHP-2/STAT1 suppression. Reversal of HLA class I downregulation was more prominent in clinical responders to cetuximab therapy, supporting an important role for adaptive immunity in cetuximab antitumor activity. Abrogating EGFR-induced immune escape mechanisms and restoring STAT1 signaling to reverse HLA downregulation using cetuximab should be combined with strategies to enhance adaptive cellular 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.