ArticleNature communications2021
Transient mTOR inhibition rescues 4-1BB CAR-Tregs from tonic signal-induced dysfunction.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Double activation and low IL-2 manufacturing protocol increase expansion of healthy and patient-derived CAR-Tregs.Molecular therapy. Advances · 2026Article
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Mapping Therapeutic Regulatory T Cell Fate with MRI: Current Strategies and Translational Outlook.Nanomaterials (Basel, Switzerland) · 2026Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Article
- Vitamin C Conditioning Generates Tumor-Targeting CAR T Cells with Superior Cytotoxicity and Fitness in a Posttransplant Lymphoproliferative Disorder Tumor Model.Molecular cancer therapeutics · 2026Article
- 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
- Roads and detours for CAR T cell therapy in autoimmune diseases.Nature reviews. Drug discovery · 2026Review
- CAR Treg therapies for neurodegenerative diseases.iScience · 2026Review
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- FOXP3 Stability-Adaptation Paradox: Reshaping Treg-Based Therapies for Intestinal Diseases.International journal of biological sciences · 2026Review
- CD8 regulatory T cell therapy in transplantation: a new path to clinical success?Transplant international : official journal of the European Society for Organ Transplantation · 2026Article
- 3-in-oneiScience · 2025Article
- Envirotune-CAR-T: a hypoxia-responsive and glutamine-enhanced CAR-T cell therapy for overcoming tumor microenvironment-mediated suppression.Journal for immunotherapy of cancer · 2025Article
- HLA-A2 CAR/IL-2-CISC engineered Treg display robustMolecular therapy. Methods & clinical development · 2025Article
- Bioengineered T-cell therapies for precision immunotherapy in renal transplantation, autoimmune relapse, and sensitization.Clinical kidney journal · 2025Review
- Revolutionizing Allogeneic Graft Tolerance Through Chimeric Antigen Receptor-T Regulatory Cells.Biomedicines · 2025Review
- Presetting CAR-T cells during ex vivo biomanufacturing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of chimeric antigen receptor (CAR)-engineered regulatory T cells (Tregs) has emerged as a promising strategy to promote immune tolerance. However, in conventional T cells (Tconvs), CAR expression is often associated with tonic signaling, which can induce CAR-T cell dysfunction. The extent and effects of CAR tonic signaling vary greatly according to the expression intensity and intrinsic properties of the CAR. Here, we show that the 4-1BB CSD-associated tonic signal yields a more dramatic effect in CAR-Tregs than in CAR-Tconvs with respect to activation and proliferation. Compared to CD28 CAR-Tregs, 4-1BB CAR-Tregs exhibit decreased lineage stability and reduced in vivo suppressive capacities. Transient exposure of 4-1BB CAR-Tregs to a Treg stabilizing cocktail, including an mTOR inhibitor and vitamin C, during ex vivo expansion sharply improves their in vivo function and expansion after adoptive transfer. This study demonstrates that the negative effects of 4-1BB tonic signaling in Tregs can be mitigated by transient mTOR inhibition.
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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.