ArticlePloS one2016
4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Elucidating the Mechanisms of SA-4-1BBL-Mediated Cancer Immunoprevention Through Advanced Informatics Approaches.Biomolecules · 2026Article
- Acasunlimab, an Fc-inert PD-L1×4-1BB bispecific antibody, combined with PD-1 blockade potentiates antitumor immunity via complementary immune modulatory effects.Journal for immunotherapy of cancer · 2025Article
- Tumor necrosis factor superfamily signaling: life and death in cancer.Cancer metastasis reviews · 2024Review
- A novel agonist of 4-1BB costimulatory receptor shows therapeutic efficacy against a tobacco carcinogen-induced lung cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Article
- A hydrogel platform for co-delivery of immunomodulatory proteins for pancreatic islet allografts.Journal of biomedical materials research. Part A · 2022Article
- Immunoprofiling of 4-1BB Expression Predicts Outcome in Chronic Lymphocytic Leukemia (CLL).Diagnostics (Basel, Switzerland) · 2021Article
- Self-driving armored CAR-T cells overcome a suppressive milieu and eradicate CD19Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Blood-Brain Barrier, Cell Junctions, and Tumor Microenvironment in Brain Metastases, the Biological Prospects and Dilemma in Therapies.Frontiers in cell and developmental biology · 2021Review
- Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors.Frontiers in cell and developmental biology · 2021Review
- Chimeric Antigen Receptor (CAR)-Modified Immune Effector Cell Therapy for Acute Myeloid Leukemia (AML).Cancers · 2020Review
- OX40L-JAG1-Induced Expansion of Lineage-Stable Regulatory T Cells Involves Noncanonical NF-κB Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus.The Journal of experimental medicine · 2019Article
- A Novel Form of 4-1BBL Prevents Cancer Development via Nonspecific Activation of CD4Cancer research · 2019Article
- A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity.Journal of autoimmunity · 2018Review
- TNF-receptor superfamily agonists as molecular adjuvants for cancer vaccines.Current opinion in immunology · 2017Review
- Amelioration of Inflammatory Cytokines Mix Stimulation: A Pretreatment of CD137 Signaling Study on VSMC.Mediators of inflammation · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Costimulation with the recombinant SA-4-1BBL agonist of 4-1BB receptor on conventional CD4+ T cells (Tconvs) overcomes the suppression mediated by naturally occurring CD4+CD25+FoxP3+ T regulatory cells (Tregs). The mechanistic basis of this observation has remained largely unknown. Herein we show that Tconvs, but not Tregs, are the direct target of SA-4-1BBL-mediated evasion of Treg suppression. IL-2 produced by Tconvs in response to 4-1BB signaling is both necessary and sufficient for overcoming Treg suppression. Supernatant from Tconvs stimulated with SA-4-1BBL contains high levels of IL-2 and overcomes Treg suppression in ex vivo Tconv:Treg cocultures. Removal of IL-2 from such supernatant restores Treg suppression and repletion of Tconv:Treg cocultures with exogenous recombinant IL-2 overcomes suppression. This study establishes 4-1BB signaling as a key circuit that regulates physical and functional equilibrium between Tregs and Tconvs with important implications for immunotherapy for indications where a fine balance between Tregs and Teffs plays a decisive role.
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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.