ArticleBlood2021
Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR-T-cell responses against ALL.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 68 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.
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.
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Who cites it
68 citing papers in PubMed, 81 citations in OpenAlex.
- The regnase family in autoimmune diseases: a regnase-1-centered perspective on cellular heterogeneity.Molecular biology reports · 2026Review
- Article
- Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma.Cell reports. Medicine · 2026Article
- Metabolic profiling of CAR T-cells in patients reveals a shift toward amino acid-supported OXPHOS and informs transporter engineering.Research square · 2026Article
- All-trans retinoic acid suppresses CD8Signal transduction and targeted therapy · 2026Article
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- Genetically modulating the RNA-binding protein Regnase-1 reveals its critical role in regulatory T cell homeostasis and function in vivo.Cell death & disease · 2026Article
- Enforced BATF expression via clinically approved LNPs enhances adoptive T-cell therapies.Blood science (Baltimore, Md.) · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Article
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- The Role of Regnase-1 in Autoimmune Diseases - A Future Therapeutic Target for Clinical Use.Clinical reviews in allergy & immunology · 2026Review
- The Regnase pathway: a core axis in immune regulation and inflammatory disease.Frontiers in immunology · 2026Review
- Regulation of T cell exhaustion and stemness: molecular mechanisms and implications for cancer immunotherapy.Cellular & molecular immunology · 2026Review
- CRISPR-screen informed engineered T cell therapies.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
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Orthogonal CRISPR systems for targeted integration and multiplex base editing enable nonviral engineering of allogeneic CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- In vivo CAR-T cell engineering: concept, research progress, potential challenges and enhancement strategies.Experimental hematology & oncology · 2025Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Chimeric antigen receptor (CAR)-T-cell therapeutic efficacy is associated with long-term T-cell persistence and acquisition of memory. Memory-subset formation requires T-cell factor 1 (TCF-1), a master transcription factor for which few regulators have been identified. Here, we demonstrate using an immune-competent mouse model of B-cell acute lymphoblastic leukemia (ALL; B-ALL) that Regnase-1 deficiency promotes TCF-1 expression to enhance CAR-T-cell expansion and memory-like cell formation. This leads to improved CAR-T-mediated tumor clearance, sustained remissions, and protection against secondary tumor challenge. Phenotypic, transcriptional, and epigenetic profiling identified increased tumor-dependent programming of Regnase-1-deficient CAR-T cells into TCF-1+ precursor exhausted T cells (TPEX) characterized by upregulation of both memory and exhaustion markers. Regnase-1 directly targets Tcf7 messenger RNA (mRNA); its deficiency augments TCF-1 expression leading to the formation of TPEX that support long-term CAR-T-cell persistence and function. Regnase-1 deficiency also reduces exhaustion and enhances the activity of TCF-1- CAR-T cells. We further validate these findings in human CAR-T cells, where Regnase-1 deficiency mediates enhanced tumor clearance in a xenograft B-ALL model. This is associated with increased persistence and expansion of a TCF-1+ CAR-T-cell population. Our findings demonstrate the pivotal roles of TPEX, Regnase-1, and TCF-1 in mediating CAR-T-cell persistence and recall responses, and identify Regnase-1 as a modulator of human CAR-T-cell longevity and potency that may be manipulated for improved therapeutic efficacy.
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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.