ArticleClinical cancer research : an official journal of the American Association for Cancer Research2017
CD137 Stimulation Enhances Cetuximab-Induced Natural Killer: Dendritic Cell Priming of Antitumor T-Cell Immunity in Patients with Head and Neck Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 123 citations in OpenAlex.
- Impact of the tumor immune contexture in microsatellite-stable metastatic colorectal cancer treated with avelumab, cetuximab, and irinotecan.Cell reports. Medicine · 2025Trial
- NK cell-mediated tumor cell killing by bispecific innate cell engagers induces ADCC-mediated activation of primary human dendritic cells.Oncoimmunology · 2026Article
- Uncovering the Potential of 3D Spheroids for Modeling the Cellular Crosstalk Within the Tumor Microenvironment in HNSCC.Biotechnology journal · 2026Review
- Dual-system engineered bacteria and dendritic cells enable precise intratumoral IL-12 delivery and potent antitumor immunity.Cell reports. Medicine · 2026Article
- Single-cell and spatial profiling reveal cDC2A-CXCL13Nature communications · 2026Article
- Characterizing the Head and Neck Cancer Microenvironment: Implications for Immunotherapy and Prognosis.Advances in experimental medicine and biology · 2026Review
- Avelumab induces greater Fc-Fc receptor-dependent natural killer cell activation and dendritic cell crosstalk compared to durvalumab.Oncoimmunology · 2025Article
- Trends in immunotherapy for oral squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Tumoricidal potential of binary therapy in lymphoma: Role of DC-NK cross-talk and checkpoint inhibitors.Histology and histopathology · 2025Review
- Immune Modulation Through KIR-HLA Interactions Influences Cetuximab Efficacy in Colorectal Cancer.International journal of molecular sciences · 2025Article
- [Research progress on the mechanisms of resistance to cetuximab targeted therapy in head and neck squamous cell carcinoma].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Article
- Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer.Nature reviews. Drug discovery · 2024Review
- Final results of urelumab, an anti-CD137 agonist monoclonal antibody, in combination with cetuximab or nivolumab in patients with advanced solid tumors.Journal for immunotherapy of cancer · 2024Article
- NK cell based immunotherapy against oral squamous cell carcinoma.Frontiers in immunology · 2024Review
- Fcγ receptors and immunomodulatory antibodies in cancer.Nature reviews. Cancer · 2024Review
- Inhibition of ATM or ATR in combination with hypo-fractionated radiotherapy leads to a different immunophenotype on transcript and protein level in HNSCC.Frontiers in oncology · 2024Article
- Natural killer cells: a future star for immunotherapy of head and neck squamous cell carcinoma.Frontiers in immunology · 2024Review
- Y-Chromosome-Linked Genes Are Associated With Sex-Related Head-Neck Squamous Cell Carcinoma Survival.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2023Article
- Perspectives in Immunotherapy: meeting report from Immunotherapy Bridge (Naples, November 30th-December 1st, 2022).Journal of translational medicine · 2023Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCetuximab, an EGFR-specific antibody (mAb), modestly improves clinical outcome in patients with head and neck cancer (HNC). Cetuximab mediates natural killer (NK) cell:dendritic cell (DC) cross-talk by cross-linking FcγRIIIa, which is important for inducing antitumor cellular immunity. Cetuximab-activated NK cells upregulate the costimulatory receptor CD137 (4-1BB), which, when triggered by agonistic mAb urelumab, might enhance NK-cell functions, to promote T-cell-based immunity. EXPERIMENTAL
designCD137 expression on tumor-infiltrating lymphocytes was evaluated in a prospective cetuximab neoadjuvant trial, and CD137 stimulation was evaluated in a phase Ib trial, in combining agonistic urelumab with cetuximab. Flow cytometry and cytokine release assays using NK cells and DC were used in vitro, testing the addition of urelumab to cetuximab-activated NK, DC, and cross presentation to T cells.
resultsCD137 agonist mAb urelumab enhanced cetuximab-activated NK-cell survival, DC maturation, and tumor antigen cross-presentation. Urelumab boosted DC maturation markers, CD86 and HLA DR, and antigen-processing machinery (APM) components TAP1/2, leading to increased tumor antigen cross-presentation. In neoadjuvant cetuximab-treated patients with HNC, upregulation of CD137 by intratumoral, cetuximab-activated NK cells correlated with FcγRIIIa V/F polymorphism and predicted clinical response. Moreover, immune biomarker modulation was observed in an open label, phase Ib clinical trial, of patients with HNC treated with cetuximab plus urelumab.
conclusionsThese results suggest a beneficial effect of combination immunotherapy using cetuximab and CD137 agonist in HNC. Clin Cancer Res; 23(3); 707-16. ©2016 AACR.
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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.