ArticleLeukemia2022
Single-cell ATAC-seq maps the comprehensive and dynamic chromatin accessibility landscape of CAR-T cell dysfunction.
Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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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Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Epigenetic insights and innovations for overcoming barriers in CAR-T cell therapy for cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- CREsted: modeling genomic and synthetic cell-type-specific enhancers across tissues and species.Nature methods · 2026Article
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Targeting CAR-T cell exhaustion in non-Hodgkin lymphoma: mechanistic insights and emerging clinical strategies.Frontiers in immunology · 2026Review
- Targeting PCNA in Cancer: A Paradigm Shift from Static Inhibition to Dynamic Network Modulation.Oncology research · 2026Review
- Remodeling of the immune microenvironment is linked to adverse outcome in pediatric T cell acute lymphoblastic leukemia.Nature communications · 2025Article
- Delving Into the Dialogue between Epigenetic Modifications and Immunometabolism in Cancer.Advanced genetics (Hoboken, N.J.) · 2025Article
- Enhancing the potency of CAR-T cells against solid tumors through transcription factor engineering.JCI insight · 2025Review
- Targeting BATF2-RGS2 axis reduces T-cell exhaustion and restores anti-tumor immunity.Molecular cancer · 2025Article
- Tumor Immunosenescence Driven by Chronic Inflammation: Mechanisms, Microenvironment Remodeling and Therapeutic Strategies.Aging and disease · 2025Review
- From Multi-Omics to Visualization and Beyond: Bridging Micro and Macro Insights in CAR-T Cell Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The impact of obesity and its related underlying diseases on cytokine release syndrome and the efficacy of CAR-T therapy in treating B-cell malignancies.Annals of hematology · 2025Article
- Innovations in immunotherapy for autoimmune diseases: recent breakthroughs and future directions.Frontiers in immunology · 2025Review
- Reshaping CAR-T cells through overexpression of T cell factor 1.Frontiers in immunology · 2025Article
- Chromatin remodeling in lymphocytic function and fate: the multifaceted roles of SWI/SNF complex.Frontiers in immunology · 2025Review
- New insights on potency assays from recent advances and discoveries in CAR T-cell therapy.Frontiers in immunology · 2025Review
- scBlood: A comprehensive single-cell accessible chromatin database of blood cells.Computational and structural biotechnology journal · 2024Article
- Targeting METTL3 as a checkpoint to enhance T cells for tumour immunotherapy.Clinical and translational medicine · 2024Article
- BRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1.Biomarker research · 2024Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor T cells (CAR-T) therapy has achieved remarkable therapeutic success in treating a variety of hematopoietic malignancies. However, the high relapse rate and poor in vivo persistence, partially caused by CAR-T cell exhaustion, are still important barriers against CAR-T therapy. It remains largely elusive on the mechanisms of CAR-T exhaustion and how to attenuate exhaustion to achieve better therapeutic efficacy. In this study, we initially observed that CAR-T cells showed rapid differentiation and increased exhaustion after co-culture with tumor cells in vitro, and then performed single-cell ATAC-seq to depict the comprehensive and dynamic landscape of chromatin accessibility of CAR-T cells during tumor cell stimulation. Analyses of differential chromatin accessible regions and motif accessibility revealed that TFs were distinct in each cell type and reconstituted a coordinated regulatory network to drive CAR-T exhaustion. Furthermore, we performed scATAC-seq in patient-derived CAR-T cells and identified BATF and IRF4 as pivotal regulators in CAR-T cell exhaustion. Finally, knockdown of BATF or IRF4 enhanced the killing ability, inhibited exhaustion, and prolonged the persistence of CAR-T cells in vivo. Together, our study unraveled the epigenetic regulatory mechanisms of CAR-T exhaustion and provided new insights into CAR-T engineering to achieve better clinical treatment benefits.
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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.