ArticleCancer discovery2023
Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T Cell-Intrinsic Dysfunction.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- CAR T-cell therapy as a definitive consolidation for older adults with B-ALL in first complete remission.Blood advances · 2026Article
- Low-Strength Type I Interferon Signaling Promotes CAR T-cell Treatment Efficacy.Cancer immunology research · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.Frontiers in immunology · 2026Review
- Rewriting CAR-T cell fate: CRISPR/Cas gene editing for solid tumor therapy.Frontiers in immunology · 2026Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities.Nature reviews. Clinical oncology · 2025Review
- Engineering the tumor microenvironment: oncolytic NDV to facilitate CAR-T cell therapy.Journal of translational medicine · 2025Review
- Soil and Seed: Tumor Microenvironment Nurtures Immunotherapy Resistance and Renewal.International journal of molecular sciences · 2025Review
- Enhancing the potency of CAR-T cells against solid tumors through transcription factor engineering.JCI insight · 2025Review
- Multifaceted regulatory mechanisms of the EGR family in tumours and prospects for therapeutic applications (Review).International journal of molecular medicine · 2025Review
- Development and optimization of Eva1 (Journal for immunotherapy of cancer · 2025Article
- CD4 T cell dysfunction is associated with bacterial recrudescence during chronic tuberculosis.Nature communications · 2025Article
- Unlocking the potential of engineered immune cell therapy for solid tumors.Nature communications · 2025Article
- CD4 T cell dysfunction is associated with bacterial recrudescence during chronic tuberculosis.bioRxiv : the preprint server for biology · 2025Article
- Article
- Augmenting antitumor efficacy of Th17-derived Th1 cells through IFN-γ-induced type I interferon response network via IRF7.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TET2 regulates early and late transitions in exhausted CD8Science advances · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapy has shown promise in treating hematologic cancers, but resistance is common and efficacy is limited in solid tumors. We found that CAR T cells autonomously propagate epigenetically programmed type I interferon signaling through chronic stimulation, which hampers antitumor function. EGR2 transcriptional regulator knockout not only blocks this type I interferon-mediated inhibitory program but also independently expands early memory CAR T cells with improved efficacy against liquid and solid tumors. The protective effect of EGR2 deletion in CAR T cells against chronic antigen-induced exhaustion can be overridden by interferon-β exposure, suggesting that EGR2 ablation suppresses dysfunction by inhibiting type I interferon signaling. Finally, a refined EGR2 gene signature is a biomarker for type I interferon-associated CAR T cell failure and shorter patient survival. These findings connect prolonged CAR T cell activation with deleterious immunoinflammatory signaling and point to an EGR2-type I interferon axis as a therapeutically amenable biological system. SIGNIFICANCE: To improve CAR T cell therapy outcomes, modulating molecular determinants of CAR T cell-intrinsic resistance is crucial. Editing the gene encoding the EGR2 transcriptional regulator renders CAR T cells impervious to type I interferon pathway-induced dysfunction and improves memory differentiation, thereby addressing major barriers to progress for this emerging class of cancer immunotherapies. This article is highlighted in the In This Issue feature, p. 1501.
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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.