ArticleImmunity2016
Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8(+) Cytolytic T Cell Responses.
Article in Immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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.
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Who cites it
107 citing papers in PubMed, 210 citations in OpenAlex.
- GSK-3 regulates CD4-CD8 cooperation for super-armed CD8+ cytolytic T cells in immunotherapy against tumors.Signal transduction and targeted therapy · 2026Article
- Low intensity vibration as a novel strategy to normalize age-related deficits in T cell proliferation, activation, and function.Scientific reports · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- From bench to bedside: navigating the clinical translation of GSK-3β inhibition in lung cancer.Medical oncology (Northwood, London, England) · 2025Article
- Glycogen Synthase Kinase 3 Is Essential for Intestinal Cell Niche and Digestive Function.Biology · 2025Article
- The mechanism and research progress of PD-1/PD-L1 on immune escape of lung cancer.Translational cancer research · 2025Review
- TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.Cell death & disease · 2025Review
- Engineered Genetic Circuits Activated by Bezafibrate Improve ESC-Based TAA Cancer Vaccine Efficacy and PD-L1 Nanobody Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Liposome-Polymer Nanoparticles Loaded with Copper Diethyldithiocarbamate and 6-Bromo-Indirubin-3'-Oxime Enable the Treatment of Refractive Melanoma.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Dual phosphorylation of glycogen synthase kinase 3β differentially integrates metabolic programs to determine T cell immunity across vertebrates.Cellular and molecular life sciences : CMLS · 2025Article
- Reply to 'Comment on: Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation'.Cellular & molecular immunology · 2025Article
- Comment on: Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation.Cellular & molecular immunology · 2025Article
- Insights into sepsis-induced apoptosis: Interplay between programmed cell death and interleukin-7.Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures) · 2025Review
- Knockout IL4I1 affects macrophages to improve poor efficacy of CD19 CAR-T combined with PD-1 inhibitor in relapsed/refractory diffuse large B-cell lymphoma.Journal of translational medicine · 2025Article
- Targeting cellular senescence in kidney diseases and aging: A focus on mesenchymal stem cells and their paracrine factors.Cell communication and signaling : CCS · 2024Review
- Podocyte senescence: from molecular mechanisms to therapeutics.Renal failure · 2024Review
- Multiomic profiling of chronically activated CD4+ T cells identifies drivers of exhaustion and metabolic reprogramming.PLoS biology · 2024Article
- Current Insights into CAR T-Cell-Based Therapies for Myelodysplastic Syndrome.Pharmaceutical research · 2024Review
- Type I Interferon Activates PD-1 Expression through Activation of the STAT1-IRF2 Pathway in Myeloid Cells.Cells · 2024Article
- Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis.Journal of biomedical science · 2024Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite the importance of the co-receptor PD-1 in T cell immunity, the upstream signaling pathway that regulates PD-1 expression has not been defined. Glycogen synthase kinase 3 (GSK-3, isoforms α and β) is a serine-threonine kinase implicated in cellular processes. Here, we identified GSK-3 as a key upstream kinase that regulated PD-1 expression in CD8(+) T cells. GSK-3 siRNA downregulation, or inhibition by small molecules, blocked PD-1 expression, resulting in increased CD8(+) cytotoxic T lymphocyte (CTL) function. Mechanistically, GSK-3 inactivation increased Tbx21 transcription, promoting enhanced T-bet expression and subsequent suppression of Pdcd1 (encodes PD-1) transcription in CD8(+) CTLs. Injection of GSK-3 inhibitors in mice increased in vivo CD8(+) OT-I CTL function and the clearance of murine gamma-herpesvirus 68 and lymphocytic choriomeningitis clone 13 and reversed T cell exhaustion. Our findings identify GSK-3 as a regulator of PD-1 expression and demonstrate the applicability of GSK-3 inhibitors in the modulation of PD-1 in immunotherapy.
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What OpenQuestion holds
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.