ArticleJournal for immunotherapy of cancer2024
NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advances, challenges, and innovative strategies of CAR-T cell therapy in pancreatic cancer.Biomarker research · 2026Review
- Emerging target antigen landscape for CAR T-cell therapy in solid tumors: current advances and future directions.Immunologic research · 2026Review
- Enhancing antitumor immunity in triple-negative breast cancer through reversal of T-cell exhaustion using a CD8-targeted and membrane-camouflaged nanocarrier delivering small interfering RNA against sorting Nexin 9.Journal of nanobiotechnology · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- KLF4 overexpression in CAR T cells enhances antitumor potency by preventing exhaustion.Journal for immunotherapy of cancer · 2026Article
- Detection of mitochondrial DNA mutations in T cells following 5-FU or cisplatin exposure.Cell reports. Medicine · 2026Article
- CD93-targeted resveratrol-loaded PLGA nanoparticles remodel CD8⁺ T cell metabolism through AIF-mediated oxidative phosphorylation to overcome lung cancer immunotherapy resistance.Journal of nanobiotechnology · 2026Article
- ITK-targeted immune remodeling enhanced the efficacy of anti-CD19 CAR-T cell therapy.Cell death discovery · 2026Article
- Targeting metabolic reprogramming to enhance adoptive immunotherapy: emerging mechanisms and translational perspectives.Journal of translational medicine · 2026Review
- PROTAC-based protein degradation: a window of opportunity for melanoma therapy.Journal of biomedical science · 2026Review
- Reversible control of T cell exhaustion by NR4A transcription factors revealed through targeted protein degradation.bioRxiv : the preprint server for biology · 2026Article
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Rewriting CAR-T cell fate: CRISPR/Cas gene editing for solid tumor therapy.Frontiers in immunology · 2026Review
- Mitochondrial reprogramming in cervical cancer: crosstalk with tumor immunity, HPV oncogenic signaling, and therapeutic resistance.Frontiers in immunology · 2026Review
- Breaking the resistance barrier: synergistic evolution of CAR-T cells and bispecific antibodies in the era of precision immuno-oncology.Frontiers in immunology · 2026Review
- Advanced strategies to enhance the safety, persistence, and efficacy of CAR-T cells in solid tumors.Frontiers in immunology · 2026Review
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- Tumor-driven stabilization of CD8Frontiers in immunology · 2026Review
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
Corrections and comments
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8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAntitumor effect of chimeric antigen receptor (CAR)-T cells against solid tumors is limited due to various factors, such as low infiltration rate, poor expansion capacity, and exhaustion of T cells within the tumor. NR4A transcription factors have been shown to play important roles in T-cell exhaustion in mice. However, the precise contribution of each NR4a factor to human T-cell differentiation remains to be clarified.
methodsIn this study, we deleted NR4A family factors,
resultsHuman NR4A-TKO CAR-T cells were resistant against exhaustion induced by repeated antigen stimulation in vitro, and maintained higher tumor-killing activity both in vitro and in vivo compared with control CAR-T cells. A comparison of the effectiveness of NR4A single, double, and TKOs demonstrated that triple KO was the most effective in avoiding exhaustion. Furthermore, a strong enhancement of antitumor effects by NR4A TKO was also observed in T cells from various donors including aged persons. Mechanistically, NR4A TKO CAR-T cells showed enhanced mitochondrial oxidative phosphorylation, therefore could persist for longer periods within the tumors.
conclusionsNR4A factors regulate CAR-T cell persistence and stemness through mitochondrial gene expression, therefore NR4A is a highly promising target for the generation of superior CAR-T cells against solid tumors.
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