ArticleProceedings of the National Academy of Sciences of the United States of America2023
Tonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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Who cites it
52 citing papers in PubMed.
- Low-dose interleukin-2 in patients with mild to moderate Alzheimer's disease: a randomized clinical trial.Alzheimer's research & therapy · 2025Trial
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Double activation and low IL-2 manufacturing protocol increase expansion of healthy and patient-derived CAR-Tregs.Molecular therapy. Advances · 2026Article
- The multifaceted landscape of T cell exhaustion in organ transplantation: From molecular mechanisms (epigenetics, transcription, metabolism) to induction strategies.Genes & diseases · 2026Review
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Manufacturing and electrostatic surface optimization of CAR-T cells improve therapeutic efficacy in liver malignancies.Hepatology communications · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Programmed death-ligand 1 on ex vivo-expanded toll-like-receptor-Bregs prevents allograft rejection by Breg viability promotion, CD4American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Adoptive T-cell therapies in the clinic.Bioengineering & translational medicine · 2026Review
- Review
- Engineered CD40-biosensor-expressing Treg cells as a cell therapy approach for inflammatory diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- CAR Treg therapies for neurodegenerative diseases.iScience · 2026Review
- Engineering programmable CAR and antigen pairing via drug-gated light activation.Nature communications · 2026Article
- Characterization of Short Production Cycle and Nongenotoxic mRNA-Based CAR-T Cells Targeting CD19-Positive and CD22-Positive Malignancies.Journal of immunology research · 2026Article
- Regulatory T cells in autoimmune diseases: biological mechanisms, clinical translation, and translational challenges.Frontiers in immunology · 2026Review
- FOXP3 Stability-Adaptation Paradox: Reshaping Treg-Based Therapies for Intestinal Diseases.International journal of biological sciences · 2026Review
- CD25Frontiers in immunology · 2026Article
- Chimeric antigen receptor T-cell therapy for rheumatic diseases: from B-cell depletion to immune reset and beyond.Frontiers in immunology · 2026Review
- Increased phenotypic and functional stability of human allospecific induced Tregs is associated with Vitamin C-mediatedFrontiers in immunology · 2026Article
- Lactic acid improves Treg manufacturing andMolecular therapy. Methods & clinical development · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Regulatory T cell (Treg) therapy is a promising approach to improve outcomes in transplantation and autoimmunity. In conventional T cell therapy, chronic stimulation can result in poor in vivo function, a phenomenon termed exhaustion. Whether or not Tregs are also susceptible to exhaustion, and if so, if this would limit their therapeutic effect, was unknown. To "benchmark" exhaustion in human Tregs, we used a method known to induce exhaustion in conventional T cells: expression of a tonic-signaling chimeric antigen receptor (TS-CAR). We found that TS-CAR-expressing Tregs rapidly acquired a phenotype that resembled exhaustion and had major changes in their transcriptome, metabolism, and epigenome. Similar to conventional T cells, TS-CAR Tregs upregulated expression of inhibitory receptors and transcription factors such as PD-1, TIM3, TOX and BLIMP1, and displayed a global increase in chromatin accessibility-enriched AP-1 family transcription factor binding sites. However, they also displayed Treg-specific changes such as high expression of 4-1BB, LAP, and GARP. DNA methylation analysis and comparison to a CD8
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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.