ArticleJournal for immunotherapy of cancer2021
Metformin generates profound alterations in systemic and tumor immunity with associated antitumor effects.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- Deciphering the Anti-Tumor Mechanisms of Metformin Through Reprogramming of the Tumor Microenvironment.Cells · 2026Review
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- Metformin drives HIF-1α-mediated dual metabolic reprogramming to enhance γδ T cell therapy in triple-negative breast cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Metformin Promotes Acquisition of Immune Tolerance in Allergen-Specific Immunotherapy.Allergy, asthma & immunology research · 2026Article
- Metformin modulates the phenotypes of tumor-associated macrophages in glioblastoma in a context-dependent manner by promoting the homeostasis of macrophages.Frontiers in oncology · 2026Article
- Metformin Sensitizes HR+/HER2- Breast Cancer Cells to CDK4/6 Inhibitor via Suppressing of PI3K/AKT/mTOR Signaling Pathway.Drug design, development and therapy · 2026Article
- Revisiting metformin as a chemotherapy adjuvant: a systematic review and meta-analysis based on recent randomized-controlled trials.Frontiers in oncology · 2026Article
- Effect of metformin on hypoxia-associated gene expression in oral cavity squamous cell carcinoma in non-diabetic patients - a prospective window of opportunity study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- Therapeutic Potential of Anti-Diabetes Drugs and Anti-Dyslipidemia Drugs to Mitigate Head and Neck Cancer Risk in Metabolic Syndrome.CNS neuroscience & therapeutics · 2025Review
- Addition of metformin to anti-PD-1/PD-L1 drugs activates anti-tumor immune response in peripheral immune cells of NSCLC patients.Cell death & disease · 2025Article
- Tobacco smoke exposure is a driver of altered oxidative stress response and immunity in head and neck cancer.Journal of translational medicine · 2025Article
- Sweet regulation - The emerging immunoregulatory roles of hexoses.Journal of advanced research · 2025Review
- Enhancing CAR-T Cell Metabolic Fitness and Memory Phenotype for Improved Efficacy against Hepatocellular Carcinoma.International journal of biological sciences · 2025Article
- Senescent immune cells in the tumor microenvironment: emerging insights into cancer immunotherapy resistance.Frontiers in immunology · 2025Review
- Drug functional remapping: a new promise for tumor immunotherapy.Frontiers in oncology · 2025Review
- Review
- Astragalus Polysaccharides and Metformin May Have Synergistic Effects on the Apoptosis and Ferroptosis of Lung Adenocarcinoma A549 Cells.Current issues in molecular biology · 2024Article
- Targeting cancer and immune cell metabolism with the complex I inhibitors metformin and IACS-010759.Molecular oncology · 2024Review
- Dependence on mitochondrial respiration of malignant T cells reveals a new therapeutic target for angioimmunoblastic T-cell lymphoma.Cell death discovery · 2024Article
- Multitarget, multiagent PLGA nanoparticles for simultaneous tumor eradication and TME remodeling in a melanoma mouse model.Drug delivery and translational research · 2024Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundMetformin is a commonly used antidiabetic medication which has demonstrated promise as an anticancer agent alone and in combination with conventional treatment regimens. There is increasing evidence that metformin can also generate immunomodulatory effects in solid tumors and is currently being investigated as an adjunct to immune checkpoint inhibitors (ICIs). We hypothesized that metformin would generate a shift in immunity unfavorable to tumor growth and tested this hypothesis in a preclinical model of head and neck cancer.
methodsUsing a syngeneic mouse model of human papillomavirus-associated head and neck cancer (mEER/MTEC), we tested the impact of metformin on systemic and local immunity and tumor growth velocity. We compared the effects of acute and chronic treatment regimens on immunocyte presence and activation using a combination of flow cytometry and targeted transcriptomic analysis.
resultsAcute metformin exposure generated measurable shifts in systemic myeloid and T-cell populations in non-tumor-bearing mice and decreased myeloid derived suppressor cell (MDSC) levels in tumor draining lymph nodes of tumor-bearing mice. Although metformin decreased regulatory T-cell (T-reg) and MDSC levels and increased CD8+ levels in murine tumors when combined with ICIs, acute metformin exposure was insufficient to generate substantial antitumor activity. Conversely, long-term metformin treatment significantly reduced tumor growth velocity, increased the CD8+/T-reg ratio, increased tumor infiltrating lymphocyte levels and upregulated component genes of the previously validated T-cell inflamed expression profile.
conclusionsMetformin generates complex systemic and local immune effects which vary as a function of treatment duration. Combinatorial strategies with ICIs must take into account both the complexity and variability of these effects in order to generate maximal antitumor activity in future clinical trials.
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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.