ArticleJournal of experimental & clinical cancer research : CR2023
Guadecitabine increases response to combined anti-CTLA-4 and anti-PD-1 treatment in mouse melanoma in vivo by controlling T-cells, myeloid derived suppressor and NK cells.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02608437 (A Phase 1b, Open-label, Dose Escalation Study Investigating Different Doses of SGI-110 in Combination With Ipilimumab in Unresectable or Metastatic Melanoma Patients), which is not on this map. Cited by 23 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 1b, Open-label, Dose Escalation Study Investigating Different Doses of SGI-110 in Combination With Ipilimumab in Unresectable or Metastatic Melanoma Patients
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Pooled it
- Current and future therapies for triple-negative breast cancer.Journal of hematology & oncology · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Review
- Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response.iScience · 2026Article
- A New Complexity Layer: DNA Methylation and the Predictive Impact of Epigenetic Tests.International journal of molecular sciences · 2026Review
- Epigenetic Modulators and Immunotherapy in Malignant Melanoma.Oncology research · 2026Review
- Epigenetic Targeting in Myeloid Malignancies.Advances in experimental medicine and biology · 2026Review
- Epigenetics of Malignant Melanoma: Mechanisms, Diagnostic Approaches and Therapeutic Applications.Oncology research · 2026Review
- Cancer and Aging Biomarkers: Classification, Early Detection Technologies and Emerging Research Trends.Biosensors · 2025Review
- Article
- Integrated multi-omics profiling reveals the role of the DNA methylation landscape in shaping biological heterogeneity and clinical behaviour of metastatic melanoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Recent advances on gene-related DNA methylation in cancer diagnosis, prognosis, and treatment: a clinical perspective.Clinical epigenetics · 2025Review
- Decitabine co-operates with the IL-33/ST2 axis modifying the tumor microenvironment and improving the response to PD-1 blockade in melanoma.Journal of experimental & clinical cancer research : CR · 2025Article
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors.Biomarker research · 2025Review
- The role of DNA methylation and demethylation in bladder cancer: a focus on therapeutic strategies.Frontiers in oncology · 2025Review
- The Trojan Horse Within: Mechanisms of Immune Evasion in Breast Cancer.Cancer heterogeneity and plasticity · 2025Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe combination of Programmed Cell Death 1 (PD-1) and Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) blockade has dramatically improved the overall survival rate for malignant melanoma. Immune checkpoint blockers (ICBs) limit the tumor's immune escape yet only for approximately a third of all tumors and, in most cases, for a limited amount of time. Several approaches to overcome resistance to ICBs are being investigated among which the addition of epigenetic drugs that are expected to act on both immune and tumor cells. Guadecitabine, a dinucleotide prodrug of a decitabine linked via phosphodiester bond to a guanosine, showed promising results in the phase-1 clinical trial, NIBIT-M4 (NCT02608437).
methodsWe used the syngeneic B16F10 murine melanoma model to study the effects of immune checkpoint blocking antibodies against CTLA-4 and PD-1 in combination, with and without the addition of Guadecitabine. We comprehensively characterized the tumor's and the host's responses under different treatments by flow cytometry, multiplex immunofluorescence and methylation analysis.
resultsIn combination with ICBs, Guadecitabine significantly reduced subcutaneous tumor growth as well as metastases formation compared to ICBs and Guadecitabine treatment. In particular, Guadecitabine greatly enhanced the efficacy of combined ICBs by increasing effector memory CD8+ T cells, inducing effector NK cells in the spleen and reducing tumor infiltrating regulatory T cells and myeloid derived suppressor cells (MDSC), in the tumor microenvironment (TME). Guadecitabine in association with ICBs increased serum levels of IFN-γ and IFN-γ-induced chemokines with anti-angiogenic activity. Guadecitabine led to a general DNA-demethylation, in particular of sites of intermediate methylation levels.
conclusionsThese results indicate Guadecitabine as a promising epigenetic drug to be added to ICBs therapy.
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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.