ArticleNature communications2021
Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02274155 (Phase Ib Study of a Monoclonal Antibody to OX40), which is not on this map. Cited by 108 papers, 2 of them syntheses that pooled it.
What it found
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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.
Phase Ib Study of a Monoclonal Antibody to OX40 (MEDI6469) Administered Prior to Definitive Surgical Resection Patients With Locoregionally Advanced, Oral Head and Neck Squamous Cell Carcinoma
Who cites it
108 citing papers in PubMed, 2 syntheses or guidelines pooled it, 153 citations in OpenAlex.
- A systematic literature review of the human papillomavirus prevalence in locally and regionally advanced and recurrent/metastatic head and neck cancers through the last decade: The "ALARM" study.Cancer medicine · 2024Pooled it
- The Roles of TNF Signaling Pathways in Metabolism of Bone Tumors.Frontiers in pharmacology · 2022Pooled it
- Trial
- Improving neoadjuvant and perioperative therapy in non-small-cell lung cancer.Nature reviews. Clinical oncology · 2026Review
- Serum metabolomics profiling in head and neck squamous cell carcinoma: a multicentre diagnostic study.EBioMedicine · 2026Article
- Host-directed immune therapies: a second front in the battle against sepsis.The Journal of clinical investigation · 2026Review
- Identification of proliferating CD103Virchows Archiv : an international journal of pathology · 2026Article
- Immunogenic tumor cell death and T-cell-derived IFN-γ elicit tumoricidal macrophages to potentiate OX40 immunotherapy.Cell reports. Medicine · 2026Article
- Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review).International journal of molecular medicine · 2026Review
- Radiation as an immune modulator: mechanisms and implications for combination with immunotherapy.Nature reviews. Cancer · 2026Review
- HFB301001, an OX40-based immunotherapy, drives Treg clearance and CTL activation through optimized OX40 receptor clustering.Journal for immunotherapy of cancer · 2026Article
- OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Next-generation immunotherapies for head and neck squamous cell carcinoma: targeting novel immune checkpoints.Annals of medicine · 2025Review
- Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.Molecular cancer · 2025Review
- Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Trends in immunotherapy for oral squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Decoding the tumor immune microenvironment in lung squamous cell carcinoma: characteristics, regulatory mechanisms, and future directions in immunotherapy.Translational lung cancer research · 2025Review
- Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas.Journal for immunotherapy of cancer · 2025Article
- Multi-omics analysis of tumor necrosis factor superfamily 4 reveals its prognostic value with T cell exhaustion feature in cancer.Discover oncology · 2025Article
- INBRX-106: a hexavalent OX40 agonist that drives superior antitumor responses via optimized receptor clustering.Journal for immunotherapy of cancer · 2025Article
48 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
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of anti-OX40 on lymphocyte subsets in the tumor and blood. Neoadjuvant anti-OX40 was well tolerated and did not delay surgery, thus meeting the primary endpoint. Peripheral blood phenotyping data show increases in CD4+ and CD8+ T cell proliferation two weeks after anti-OX40 administration. Comparison of tumor biopsies before and after treatment reveals an increase of activated, conventional CD4+ tumor-infiltrating lymphocytes (TIL) in most patients and higher clonality by TCRβ sequencing. Analyses of CD8+ TIL show increases in tumor-antigen reactive, proliferating CD103+ CD39+ cells in 25% of patients with evaluable tumor tissue (N = 4/16), all of whom remain disease-free. These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. Our work suggests that increases in the tumor-reactive CD103+ CD39+ CD8+ TIL could serve as a potential biomarker of anti-OX40 clinical activity.
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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.