ArticleFrontiers in immunology2021
Dissecting the Role of BET Bromodomain Proteins BRD2 and BRD4 in Human NK Cell Function.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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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
17 citing papers in PubMed, 37 citations in OpenAlex.
- Bromodomain and extra-terminal protein inhibitors modulate natural killer cell function and differentiation.Scientific reports · 2026Article
- Identifying ARRB2 as a Prognostic Biomarker and Key Player in the Tumor Microenvironment of Pancreatic Cancer through scPagwas Methodology.Current gene therapy · 2026Article
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
- Multi-Omics Mendelian Randomization Identifies Therapeutic Targets for Sjögren's Disease with Clinical and Bayesian Validation.Journal of inflammation research · 2025Article
- Personalized immunization to optimize vaccine immunogenicity: exploring the multidimensional effects of host intrinsic factors, external intervention strategies, and the external environment.Frontiers in immunology · 2025Review
- Unraveling the Role of Bromodomain and Extra-Terminal Proteins in Human Uterine Leiomyosarcoma.Cells · 2024Article
- BET inhibitors drive Natural Killer activation in non-small cell lung cancer via BRD4 and SMAD3.Nature communications · 2024Article
- The BET degrader ZBC260 suppresses stemness and tumorigenesis and promotes differentiation in triple-negative breast cancer by disrupting inflammatory signaling.Breast cancer research : BCR · 2023Article
- First-in-human Study of AZD5153, A Small-molecule Inhibitor of Bromodomain Protein 4, in Patients with Relapsed/Refractory Malignant Solid Tumors and Lymphoma.Molecular cancer therapeutics · 2023Article
- Single-cell RNA-seq reveals a microenvironment and an exhaustion state of T/NK cells in acute myeloid leukemia.Cancer science · 2023Article
- Epigenetics behind tumor immunology: a mini review.Oncogene · 2023Review
- Differential responses of pulmonary vascular cells from PAH patients and controls to TNFα and the effect of the BET inhibitor JQ1.Respiratory research · 2023Article
- Effects of epigenetic therapy on natural killer cell function and development in hematologic malignancy.Journal of leukocyte biology · 2023Review
- Butyrate limits human natural killer cell effector function.Scientific reports · 2023Article
- Regulation of short-chain fatty acids in the immune system.Frontiers in immunology · 2023Review
- Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheumatoid Arthritis.Cells · 2021Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Natural killer (NK) cells are innate lymphocytes that play a pivotal role in the immune surveillance and elimination of transformed or virally infected cells. Using a chemo-genetic approach, we identify BET bromodomain containing proteins BRD2 and BRD4 as central regulators of NK cell functions, including direct cytokine secretion, NK cell contact-dependent inflammatory cytokine secretion from monocytes as well as NK cell cytolytic functions. We show that both BRD2 and BRD4 control inflammatory cytokine production in NK cells isolated from healthy volunteers and from rheumatoid arthritis patients. In contrast, knockdown of BRD4 but not of BRD2 impairs NK cell cytolytic responses, suggesting BRD4 as critical regulator of NK cell mediated tumor cell elimination. This is supported by pharmacological targeting where the first-generation pan-BET bromodomain inhibitor JQ1(+) displays anti-inflammatory effects and inhibit tumor cell eradication, while the novel bivalent BET bromodomain inhibitor AZD5153, which shows differential activity towards BET family members, does not. Given the important role of both cytokine-mediated inflammatory microenvironment and cytolytic NK cell activities in immune-oncology therapies, our findings present a compelling argument for further clinical investigation.
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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.