Trial reportThe Journal of experimental medicine2023
IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma.
Trial report in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Updated pan-tumor guidelines for neoadjuvant scoring of pathologic response: a joint SITC and INMC effort.Annals of oncology : official journal of the European Society for Medical Oncology · 2026Guideline
- Spatial architecture contributes to failure of bulk biomarker-guided neoadjuvant immunotherapy selection in bladder cancer: The DUTRENEO study.Cell reports. Medicine · 2026Trial
- Neoadjuvant ipilimumab plus nivolumab in melanoma: 5-year survival and biomarker analysis from the phase 2 PRADO-trial.Nature medicine · 2026Trial
- Neoadjuvant ipilimumab and nivolumab in resectable cutaneous squamous cell carcinoma: a randomized phase 2 trial.Nature medicine · 2025Trial
- A Phase II Study of Perioperative Avelumab plus Chemotherapy for Patients with Resectable Gastric Cancer or Gastroesophageal Junction Cancer - The MONEO Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Pretreatment and on-treatment ctDNA and tissue biomarkers predict recurrence in patients with stage IIIB-D/IV melanoma treated with adjuvant immunotherapy: CheckMate 915.Journal for immunotherapy of cancer · 2025Trial
- Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.Nature medicine · 2025Trial
- Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial.Nature medicine · 2024Trial
- Review
- Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial.Nature medicine · 2026Article
- Concordance of pathologic response assessment between local and central review in melanoma: a post hoc analysis of KEYMAKER-U02 substudy 02C.ESMO open · 2026Article
- Review
- Lessons from neoadjuvant immunotherapy in melanoma: understanding antitumour immunity and tumour escape.Nature reviews. Immunology · 2026Review
- Dual role of IFNγ in reprogramming the undifferentiated pleomorphic sarcoma cell line JBT19 towards cytotoxic chemotherapy and antitumor immunity.Oncology letters · 2026Article
- After a Decade of Therapy Revolution in Cutaneous Melanoma-Perspectives on Emerging Treatment Strategies.Oncology research · 2026Review
- Epigenetics of Malignant Melanoma: Mechanisms, Diagnostic Approaches and Therapeutic Applications.Oncology research · 2026Review
- Toward Personalized Response Monitoring in Melanoma Patients Treated with Immunotherapy and Target Therapy.Diagnostics (Basel, Switzerland) · 2025Review
- Circulating IFNγ-associated protein signatures predict response to neoadjuvant immunotherapy in patients with stage III melanoma.Cancer cell international · 2025Article
- Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.Experimental hematology & oncology · 2025Review
- The rapidly evolving paradigm of neoadjuvant immunotherapy across cancer types.Nature cancer · 2025Review
Corrections and comments
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Authors and funding
26 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neoadjuvant ipilimumab + nivolumab has demonstrated high pathologic response rates in stage III melanoma. Patients with low intra-tumoral interferon-γ (IFN-γ) signatures are less likely to benefit. We show that domatinostat (a class I histone deacetylase inhibitor) addition to anti-PD-1 + anti-CTLA-4 increased the IFN-γ response and reduced tumor growth in our murine melanoma model, rationalizing evaluation in patients. To stratify patients into IFN-γ high and low cohorts, we developed a baseline IFN-γ signature expression algorithm, which was prospectively tested in the DONIMI trial. Patients with stage III melanoma and high intra-tumoral IFN-γ scores were randomized to neoadjuvant nivolumab or nivolumab + domatinostat, while patients with low IFN-γ scores received nivolumab + domatinostat or ipilimumab + nivolumab + domatinostat. Domatinostat addition to neoadjuvant nivolumab ± ipilimumab did not delay surgery but induced unexpected severe skin toxicity, hampering domatinostat dose escalation. At studied dose levels, domatinostat addition did not increase treatment efficacy. The baseline IFN-γ score adequately differentiated patients who were likely to benefit from nivolumab alone versus patients who require other therapies.
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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.