ArticleMolecular cancer2021
AMPK promotes antitumor immunity by downregulating PD-1 in regulatory T cells via the HMGCR/p38 signaling pathway.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- AMPK-Mediated Lipid Metabolic Reprogramming in Cancer: From Mechanisms to Targeted Therapies.Cell biochemistry and function · 2026Review
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.Translational lung cancer research · 2026Review
- Dendrobium officinale polysaccharide ameliorate hyperlipidemia through LKB1/AMPK and CD36/PGC-1α/UCP1 activation and gut microbiota modulation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- [Heterogeneity of Response to PD-1/PD-L1 Inhibitors in Elderly Patients with Advanced NSCLC under the Background of Immunosenescence and Intervention Strategies].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Systems pharmacology approaches decipher the anti-cancer efficacy of ethnopharmacological agents in hepatocellular carcinoma.Scientific reports · 2025Article
- Unveiling the potential benefits of statins in medulloblastoma treatment: A promising therapeutic approach.IBRO neuroscience reports · 2025Review
- Targeting cholesterol metabolism: a promising therapy strategy for cancer.Acta pharmacologica Sinica · 2025Review
- PBX3-HMGCR Axis Promotes Hepatocellular Carcinoma Progression Through Enhancing De Novo Cholesterol Biosynthesis.International journal of molecular sciences · 2025Article
- AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia.The Journal of clinical investigation · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- Ferroptosis of T cell in inflammation and tumour immunity.Clinical and translational medicine · 2025Review
- HBV-associated hepatocellular carcinomas inhibit antitumor CD8Nature communications · 2025Article
- A biodegradable capacitive-coupling neurostimulator for wireless electroceutical treatment of inflammatory bowel diseases.Science advances · 2025Article
- Puerarin as a multi-targeted modulator of lipid metabolism: molecular mechanisms, therapeutic potential and prospects for nutritional translation.Frontiers in nutrition · 2025Review
- Immunomodulatory therapy for sepsis: from pathophysiological mechanisms to precision treatment.Frontiers in cellular and infection microbiology · 2025Review
- HMGCR: a malignancy hub - frontiers in cancer diagnosis and therapy.Frontiers in oncology · 2025Review
- Targeting AMPK for Cancer Therapy: Metabolic Reprogramming as a Therapeutic Strategy.Oncology research · 2025Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAMP-activated protein kinase (AMPK) is a metabolic sensor that maintains energy homeostasis. AMPK functions as a tumor suppressor in different cancers; however, its role in regulating antitumor immunity, particularly the function of regulatory T cells (Tregs), is poorly defined.
methodsAMPKα1
resultsThe deletion of the AMPKα1 subunit in Tregs accelerates tumor growth by increasing the expression of PD-1. Metabolically, loss of AMPK in Tregs promotes glycolysis and the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme of the mevalonate pathway. Mechanistically, AMPK activates the p38 mitogen-activated protein kinase (MAPK) that phosphorylates glycogen synthase kinase-3β (GSK-3β), inhibiting the expression of PD-1 in Tregs.
conclusionOur study identified an AMPK regulatory mechanism of PD-1 expression via the HMGCR/p38 MAPK/GSK3β signaling pathway. We propose that the AMPK activator can display synergic antitumor effect in murine tumor models, supporting their potential clinical use when combined with anti-PD-1 antibody, anti-CTLA-4 antibody, or a HMGCR inhibitor.
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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.