ArticleNature cancer2023
Disrupting the phase separation of KAT8-IRF1 diminishes PD-L1 expression and promotes antitumor immunity.
Article in Nature cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers, 1 of them a synthesis that pooled it.
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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
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Pooled it
- Nanoadjuvant-based membrane poration boosts antitumor immunity via modulating mitochondrial metabolism to downregulate PD-L1 and upregulate STING.Bioactive materials · 2027Article
- Low circulating miR-5193 promotes PD-L1-mediated immune evasion and relates to immune checkpoint inhibitor response in esophageal cancer.Molecular therapy. Nucleic acids · 2026Article
- KAT8-mediated epigenetic modifications: Physiological functions, heterogeneity in disease, and advances in targeted development.iScience · 2026Review
- Functionalized Coacervates for Cancer Therapy: Advances and Prospects in Phase-Separation-Based Intelligent Drug Delivery.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- An immunogenomic classification of solid tumours reveals subtype-specific therapeutic vulnerabilities for immunotherapy.EBioMedicine · 2026Article
- Dysregulation of liquid-liquid phase separation: from molecular mechanisms to targeted therapies in cardiovascular diseases.Journal of nanobiotechnology · 2026Review
- Disrupting SOX2 self-association and condensate formation to overcome chemotherapeutic drug resistance in lung squamous cell carcinoma.Signal transduction and targeted therapy · 2026Article
- Small molecules modulate the biomolecular condensates and liquid‒liquid phase separation.Acta pharmaceutica Sinica. B · 2026Review
- Targeting IRF1-TRIM21 axis enhances anti-tumor immunity by promoting ubiquitin-mediated degradation of FGL1 in non-small cell lung cancer.Communications biology · 2026Article
- Liquid-liquid phase separation in cancer therapy resistance.iScience · 2026Review
- Characterization and regulatory mechanism evaluation of C8orf33 in hepatocellular carcinoma through multiomics profiling.Discover oncology · 2026Article
- Reinforced immunotherapy of M1 macrophage-derived exosomes with CEL on TNBC via regulating macrophage functions.Journal of advanced research · 2026Article
- Novel insights into extracellular vesicles: An update on biomolecules, immunomodulation and clinical strategies in skin melanoma.Clinical and translational medicine · 2026Review
- G3BP2-K76 acetylation promotes tumor immunoescape by stabilizing PD-L1 expression in colorectal cancer.Cell communication and signaling : CCS · 2026Article
- Lactylation at lysine 145 fosters KAT8-TIP60 complex formation to promote p53 acetylation at lysine 120 and its pro-apoptotic function.Nature communications · 2026Article
- Phase separation of DDHD2 remodels lipid metabolism to dictate treatment sensitivity in luminal breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Low-dose radiotherapy remodels the tumor immune microenvironment via the cGAS-STING pathway: mechanisms, challenges, and combination therapy strategies.Molecular cancer · 2026Review
- AGPAT3 reshapes tumor cell vulnerability to IFNγ-mediated ferroptosis and enhances immunotherapy efficacy through lipid remodeling.Journal for immunotherapy of cancer · 2026Article
- Pharmacological targeting of oncogenic condensates in cancer: mechanistic insights and therapeutic opportunities.Acta pharmacologica Sinica · 2026Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapies targeting the PD-1/PD-L1 axis have become first-line treatments in multiple cancers. However, only a limited subset of individuals achieves durable benefits because of the elusive mechanisms regulating PD-1/PD-L1. Here, we report that in cells exposed to interferon-γ (IFNγ), KAT8 undergoes phase separation with induced IRF1 and forms biomolecular condensates to upregulate PD-L1. Multivalency from both the specific and promiscuous interactions between IRF1 and KAT8 is required for condensate formation. KAT8-IRF1 condensation promotes IRF1 K78 acetylation and binding to the CD247 (PD-L1) promoter and further enriches the transcription apparatus to promote transcription of PD-L1 mRNA. Based on the mechanism of KAT8-IRF1 condensate formation, we identified the 2142-R8 blocking peptide, which disrupts KAT8-IRF1 condensate formation and consequently inhibits PD-L1 expression and enhances antitumor immunity in vitro and in vivo. Our findings reveal a key role of KAT8-IRF1 condensates in PD-L1 regulation and provide a competitive peptide to enhance antitumor immune responses.
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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.