ArticlePLoS biology2018
KDM5 histone demethylases repress immune response via suppression of STING.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
120 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- ACE2 Expression Is Increased in the Lungs of Patients With Comorbidities Associated With Severe COVID-19.The Journal of infectious diseases · 2020Pooled it
- Targeting the Chromatin-Modifying Enzyme, KDM5C, Enhances AKT Inhibition Response in ER+ Breast Cancer.Molecular cancer therapeutics · 2026Article
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Kdm2a histone demethylase ablation restores anti-tumor immunogenicity in liver cancer.British journal of cancer · 2026Article
- Dual Role of Tamoxifen in Enhancing STING and CEACAM1 Expression to Prime a Favorable Tumor Microenvironment for Anti-TIM3 Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DHRS9 generates crotonyl-CoA from butyryl-CoA to epigenetically regulate STING transcription and potentiate immune activation.Cell death and differentiation · 2026Article
- Discovery of XNW5004 as a novel EZH2 inhibitor that enhances anti-tumor immunity and synergizes with PD-1 blockade immunotherapy in lung adenocarcinoma.Journal of translational medicine · 2026Article
- Epigenetic mechanisms of inflammatory memory in the central nervous system.Nature immunology · 2026Review
- JQKD82 Inhibits HIV Infection of Macrophages Through Blocking Viral Entry and Enhancing Antiviral ISG Responses.Journal of medical virology · 2026Article
- PCGF1-mediated bivalent promoter remodeling enables NK cell immune evasion in non-small cell lung cancer.Cell death & disease · 2026Article
- Polyelectrolyte nanoparticles enable intracellular delivery of STING protein fragments for ovarian cancer immunotherapy.Materials today. Bio · 2026Article
- PBRM1 Deficiency Reshapes an Immune Suppressive Microenvironment Through Epigenetic Tuning of PBRM1-KDM5C-IL6 Axis in ccRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nanomedicine leverages cuproptosis-mediated cGAS-STING activation to enhance antitumor immunity.Journal of nanobiotechnology · 2026Review
- ERRα-KDM5C restrains STING enhancer activity to modulate type I interferon signaling in breast cancer progression.Cell death & disease · 2026Article
- KDM5B cooperates with CRL4B complex to promote the tumorigenesis of ER+ breast cancer via regulating cholesterol metabolism.Cell death & disease · 2026Article
- Precision targeting of STING: Challenges, innovations, and clinical outlook for cancer therapy.Innovation (Cambridge (Mass.)) · 2026Review
- cGAS-STING and PANoptosis: Interplay, Underlying Mechanisms, and Therapeutic Targets.Drug design, development and therapy · 2026Review
- Emerging role ofFrontiers in molecular neuroscience · 2026Article
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 2 countries.
Funding
Abstract
Cyclic GMP-AMP (cGAMP) synthase (cGAS) stimulator of interferon genes (STING) senses pathogen-derived or abnormal self-DNA in the cytosol and triggers an innate immune defense against microbial infection and cancer. STING agonists induce both innate and adaptive immune responses and are a new class of cancer immunotherapy agents tested in multiple clinical trials. However, STING is commonly silenced in cancer cells via unclear mechanisms, limiting the application of these agonists. Here, we report that the expression of STING is epigenetically suppressed by the histone H3K4 lysine demethylases KDM5B and KDM5C and is activated by the opposing H3K4 methyltransferases. The induction of STING expression by KDM5 blockade triggered a robust interferon response in a cytosolic DNA-dependent manner in breast cancer cells. This response resulted in resistance to infection by DNA and RNA viruses. In human tumors, KDM5B expression is inversely associated with STING expression in multiple cancer types, with the level of intratumoral CD8+ T cells, and with patient survival in cancers with a high level of cytosolic DNA, such as human papilloma virus (HPV)-positive head and neck cancer. These results demonstrate a novel epigenetic regulatory pathway of immune response and suggest that KDM5 demethylases are potential targets for antipathogen treatment and anticancer immunotherapy.
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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.