ArticleGut2025
Pharmacological activation of STAT1-GSDME pyroptotic circuitry reinforces epigenetic immunotherapy for hepatocellular carcinoma.
Article in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 28 papers.
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 Clinical Trial of Pembrolizumab in Patients With Hepatitis B Virus-related Hepatocellular Carcinoma, With Parallel Study on Baseline and Serial Change in the Immune Environment
Epigenetic Therapeutics to Overcome Resistance Against Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: A Proof-of-concept Clinical Trial
Who cites it
28 citing papers in PubMed.
- Spatially organized regulated cell death-immune coupling in solid tumors: integrating spatial omics with actionable regulated cell death biology.Molecular cancer · 2026Review
- Gasdermin E: Bridging Pyroptosis, Immunity, and Disease Pathogenesis Toward Precision Intervention.The protein journal · 2026Review
- Targeting the cytokine-epigenetic axis: a new paradigm and prospects for disease treatment.European cytokine network · 2026Review
- Epigenetic orchestration of cancer-immune dynamics: mechanisms, technologies, and clinical advancements.Journal of advanced research · 2026Review
- Overcoming MDSC-Mediated Immunosuppression in Hepatocellular Carcinoma: From Mechanisms to Novel Immunotherapeutic Approaches.Cancers · 2026Review
- Pan-cancer analysis reveals HDAC1 as a key regulator of immune infiltration and T cell exhaustion.Discover oncology · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Targeting G9a Exerts Pleiotropic Suppression in Triple-Negative Breast Cancer Cells: Cooperatively Inducing Pyroptosis and Apoptosis.Biomolecules · 2026Article
- The molecular mechanisms of pyroptosis and its implications in tumor immunotherapy.Molecular cancer · 2026Review
- Inhibition of LDHA promotes GSDME-dependent pyroptosis by activating RIG-I-like receptor signaling.Apoptosis : an international journal on programmed cell death · 2026Article
- Overcoming immune resistance in hepatocellular carcinoma: insights into mechanisms, predictive factors, and interventional strategies.Frontiers in immunology · 2026Review
- Exploring the prognostic value of T cell exhaustion and mitochondrial dysfunction related genes in breast cancer through bioinformatics analysis and RT-qPCR validation.Clinical and experimental medicine · 2025Article
- Genome-wide CRISPR screen identifies splicing factor SF3B4 in driving hepatocellular carcinoma.Science advances · 2025Article
- Combination immunotherapy in hepatocellular carcinoma: synergies among immune checkpoints, TKIs, and chemotherapy.Journal of hematology & oncology · 2025Review
- FADD Activation in Hepatocellular Carcinoma Potentiates CD8+ T-cell Responses and Sensitizes to Immune Checkpoint Inhibitors.Cancer research · 2025Article
- Debates and progress in the management of intermediate-stage (BCLC stage B) hepatocellular carcinoma.iLIVER · 2025Review
- Review
- The HDAC inhibitor romidepsin renders liver cancer vulnerable to RTK targeting and immunologically active.Nature communications · 2025Article
- STAT1β modulates the tumor immune microenvironment to improve prognosis in ovarian cancer: a comprehensive study of transcriptional and protein expression differences.Journal of ovarian research · 2025Article
- Expression landscape of epigenetic genes in human hepatocellular carcinoma.Journal of physiology and biochemistry · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenomic screening uncovered interferon-gamma (IFNγ) pathway defects in tumours refractory to immune checkpoint blockade (ICB). However, its non-mutational regulation and reversibility for therapeutic development remain less understood.
objectiveWe aimed to identify ICB resistance-associated druggable histone deacetylases (HDACs) and develop a readily translatable combination approach for patients with hepatocellular carcinoma (HCC).
designWe correlated the prognostic outcomes of HCC patients from a pembrolizumab trial (NCT03419481) with tumourous cell expressions of all HDAC isoforms by single-cell RNA sequencing. We investigated the therapeutic efficacy and mechanism of action of selective HDAC inhibition in 4 ICB-resistant orthotopic and spontaneous models using immune profiling, single-cell multiomics and chromatin immunoprecipitation-sequencing and verified by genetic modulations and co-culture systems.
resultsHCC patients showing higher
conclusionOur immunoepigenetic strategy harnesses IFNγ-mediated network to augment the cancer-immunity cycle, revealing a self-reinforcing STAT1-GSDME pyroptotic circuitry as the mechanistic basis for an ongoing phase-II trial to tackle ICB resistance (NCT05873244).
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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.