ArticleThe Journal of clinical investigation2025
Epigenetic therapy sensitizes anti-PD-1 refractory head and neck cancers to immunotherapy rechallenge.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03019003 (A Phase IB Rescue Study With Oral Decitabine), which is not on this map. Cited by 16 papers, 1 of them a synthesis 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.
A Phase IB Rescue Study With Oral Decitabine (AStX727) and Durvalumab (MEDI4736) Combination Therapy in Recurrent and/or Metastatic Head and Neck Cancer Patients Who Have Progressed on Anti-PD-1, Anti-PD-L1, or Anti-CTLA-4 Monotherapy
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Advancing immune checkpoint inhibitor rechallenge: key insights into efficacy, safety, and personalized strategies in advanced solid tumors.Frontiers in oncology · 2026Pooled it
- Head and neck squamous cell carcinoma: current and emerging therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.NPJ precision oncology · 2026Article
- Epigenetic alterations in head and neck cancer: a brief update.Virchows Archiv : an international journal of pathology · 2026Review
- Review
- Prognostic value of DNA methylation in head and neck cancer: a systematic review and meta-analysis.Translational cancer research · 2026Article
- Integrating interferon gamma receptor pathways, antigenicity, and immune contexture as predictors of immunotherapeutic strategies for mucosal melanomas.Journal for immunotherapy of cancer · 2026Article
- Identification of core cytotoxic T lymphocyte-related subtypes, establishment of a prognostic model, and analysis tumor microenvironment infiltration in HNSC.Scientific reports · 2026Article
- Immunotherapy in Head and Neck Cancer-Where Are We Now and Where Are We Headed?International journal of molecular sciences · 2026Review
- Inducing tumor-intrinsic innate immune response to break cancer immunotherapy resistance.Frontiers in medicine · 2026Review
- The IFN-γ response cycle: decoupling tumor killing from evolutionary selection in cancer immunotherapy.Frontiers in immunology · 2026Review
- Head and Neck Cancer Immunotherapy: Overcoming Limitations and Enhancing Efficacy.Cancer science · 2025Review
- CD8 T cells mediate immunosurveillance for neoantigen+ epithelial stem cells in the colon.bioRxiv : the preprint server for biology · 2025Article
- Association of HPV in the Genesis of Head and Neck Squamous Cell Carcinoma: A Case-Control Study in a Bulgarian Cohort.Cancers · 2025Article
- Novel Therapeutic Strategies for Squamous Cell Carcinoma of the Head and Neck: Beyond EGFR and Checkpoint Blockade.Biomedicines · 2025Review
- Metabolic reprogramming and immune microenvironment characteristics in laryngeal carcinoma: advances in immunotherapy.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
Abstract
BACKGROUNDImmune checkpoint blockade (ICB) is an effective treatment in a subset of patients diagnosed with head and neck squamous cell carcinoma (HNSCC); however, the majority of patients are refractory.METHODSIn a nonrandomized, open-label Phase 1b clinical trial, participants with recurrent and/or metastatic (R/M) HNSCC were treated with low-dose 5-azacytidine (5-aza) daily for either 5 or 10 days in combination with durvalumab and tremelimumab after progression on ICB. The primary objective was to assess the biologically effective dose of 5-aza as determined by molecular changes in paired baseline and on-treatment tumor biopsies; the secondary objective was safety.RESULTSThirty-eight percent (3 of 8) of participants with evaluable paired tissue samples had a greater-than 2-fold increase from baseline in IFN-γ signature and CD274 (programmed cell death protein 1 ligand, PD-L1) expression within the tumor microenvironment (TME), which was associated with increased CD8+ T cell infiltration and decreased infiltration of CD4+ T regulatory cells. The mean neutrophil-to-lymphocyte ratio (NLR) decreased by greater than 50%, from 14.2 (SD 22.6) to 6.9 (SD 5.2). Median overall survival (OS) was 16.3 months (95% CI 1.9, NA), 2-year OS rate was 24.7% (95% CI: 4.5%, 53.2%), and 58% (7 of 12) of treated participants demonstrated prolonged OS of greater than 12 months.CONCLUSIONOur findings suggest that low-dose 5-aza can reprogram systemic host immune responses and the local TME to increase IFN-γ and PD-L1 expression. The increased expression of these established biomarkers correlated with prolonged OS upon ICB rechallenge.TRIAL REGISTRATIONClinicalTrials.gov NCT03019003.FUNDINGNIH/NCI P01 CA240239.
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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.