ArticleThe Journal of clinical investigation2016
BET bromodomain inhibition enhances T cell persistence and function in adoptive immunotherapy models.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed, 211 citations in OpenAlex.
- Short-chain fatty acids act as metabolic and epigenetic regulators in CAR T cell therapy.Molecular therapy. Oncology · 2026Review
- Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.Clinical and experimental medicine · 2026Review
- Epigenetic reprogramming of T cell metabolism restores function and enhances anti-tumor immunity in lung cancer.Nature immunology · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Epigenetic orchestration of cancer-immune dynamics: mechanisms, technologies, and clinical advancements.Journal of advanced research · 2026Review
- CD28-driven ex vivo generation of stem-like memory CD8Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Employing epigenetic protein degradation techniques to block CCL5-mediated photodynamic therapy via a programmed delivery platform.Signal transduction and targeted therapy · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- BET bromodomain inhibition potentiates antitumor activity of tumor-associated macrophages and enhances anti-CD47 immunotherapy in triple-negative breast cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Dual Bcl-2/Bcl-xl inhibition via AZD0466 combines with immune checkpoint blockade to enhance anti-tumour activity.Cell death & disease · 2026Article
- Developing immunotherapies through glycosylation reprogramming to combat solid cancers.Frontiers in immunology · 2026Review
- Regulation of T cell exhaustion and stemness: molecular mechanisms and implications for cancer immunotherapy.Cellular & molecular immunology · 2026Review
- The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.Journal for immunotherapy of cancer · 2025Review
- BACH2 promotes seeding and establishment of long-lived HIV-1 reservoir in memory CD4Cell reports. Medicine · 2025Article
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- The role of BATF in immune cell differentiation and autoimmune diseases.Biomarker research · 2025Review
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
- Therapeutic potential of tumor-infiltrating lymphocytes in non-small cell lung cancer.Cancer letters · 2024Review
- BRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1.Biomarker research · 2024Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Adoptive immunotherapy is a potentially curative therapeutic approach for patients with advanced cancer. However, the in vitro expansion of antitumor T cells prior to infusion inevitably incurs differentiation towards effector T cells and impairs persistence following adoptive transfer. Epigenetic profiles regulate gene expression of key transcription factors over the course of immune cell differentiation, proliferation, and function. Using comprehensive screening of chemical probes with defined epigenetic targets, we found that JQ1, an inhibitor of bromodomain and extra-terminal motif (BET) proteins, maintained CD8+ T cells with functional properties of stem cell-like and central memory T cells. Mechanistically, the BET protein BRD4 directly regulated expression of the transcription factor BATF in CD8+ T cells, which was associated with differentiation of T cells into an effector memory phenotype. JQ1-treated T cells showed enhanced persistence and antitumor effects in murine T cell receptor and chimeric antigen receptor gene therapy models. Furthermore, we found that histone acetyltransferase p300 supported the recruitment of BRD4 to the BATF promoter region, and p300 inhibition similarly augmented antitumor effects of the adoptively transferred T cells. These results demonstrate that targeting the BRD4-p300 signaling cascade supports the generation of superior antitumor T cell grafts for adoptive 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.