ArticleProceedings of the National Academy of Sciences of the United States of America2015
Immune-mediated antitumor effect by type 2 diabetes drug, metformin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04387630 (Neoadjuvant Chemotherapy With or Without Metformin in Early Breast Cancer.), which is not on this map. Cited by 344 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.
Neoadjuvant Chemotherapy With or Without Metformin in Early Breast Cancer.
Who cites it
344 citing papers in PubMed.
- Phase II trial of nivolumab and metformin in patients with treatment-refractory microsatellite stable metastatic colorectal cancer.Journal for immunotherapy of cancer · 2023Trial
- Targeted PD-L1 degradation with an injectable hydrogel reverses chemotherapy-induced compensatory immunosuppression and enhances antitumor immunity.Materials today. Bio · 2026Article
- Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives.Biomedicines · 2026Review
- Uncovering the Potential of 3D Spheroids for Modeling the Cellular Crosstalk Within the Tumor Microenvironment in HNSCC.Biotechnology journal · 2026Review
- Anti-PD-1 Treatment Restores Effector Function in Exhausted-like T Cells from Malignant Ascites of Ovarian Cancer Patients.Cancers · 2026Article
- Proton Pump Inhibitor Use and Survival Outcomes in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Immunotherapy: A Real-World Study.Medicina (Kaunas, Lithuania) · 2026Article
- Article
- p53 and p21 Status Influences Cellular Response to Metformin inCurrent issues in molecular biology · 2026Article
- Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.Biomarker research · 2026Review
- Autophagy-promoted immunogenic cell death elicited by tyrosine kinase inhibitor orchestrates a synergistic immunotherapeutic microenvironment in hepatocellular carcinoma.Experimental hematology & oncology · 2026Article
- Review
- Metformin enhances survival with immune checkpoint inhibitors in cancer patients: A meta-analysis.Oncology letters · 2026Article
- Metformin-A Type 2 Diabetes Mellitus Drug-And Ovarian Cancer: Anticancer Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- From Metabolism to Longevity: Molecular Mechanisms Underlying Metformin's Anticancer and Anti-Aging Effects.Current issues in molecular biology · 2026Review
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Metformin Promotes Acquisition of Immune Tolerance in Allergen-Specific Immunotherapy.Allergy, asthma & immunology research · 2026Article
- CAR-T therapy in non-small cell lung cancer: Clinical prospects, potential, and strategies for cardiotoxicity management.Translational oncology · 2026Article
- Intermittent fasting enhances cisplatin-metformin efficacy in therapy-resistant ovarian cancer PDXs.iScience · 2026Article
- Mitochondrial Energy Metabolism in Cancer, Immunoregulation and Antitumour Response.Advances in experimental medicine and biology · 2026Review
- Mitochondrial transfer in the tumor microenvironment: a dynamic determinant of cancer plasticity, immune dysfunction, and therapeutic opportunity.Frontiers in immunology · 2026Review
284 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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin, a prescribed drug for type 2 diabetes, has been reported to have anti-cancer effects; however, the underlying mechanism is poorly understood. Here we show that this mechanism may be immune-mediated. Metformin enabled normal but not T-cell-deficient SCID mice to reject solid tumors. In addition, it increased the number of CD8(+) tumor-infiltrating lymphocytes (TILs) and protected them from apoptosis and exhaustion characterized by decreased production of IL-2, TNFα, and IFNγ. CD8(+) TILs capable of producing multiple cytokines were mainly PD-1(-)Tim-3(+), an effector memory subset responsible for tumor rejection. Combined use of metformin and cancer vaccine improved CD8(+) TIL multifunctionality. The adoptive transfer of antigen-specific CD8(+) T cells treated with metformin concentrations as low as 10 μM showed efficient migration into tumors while maintaining multifunctionality in a manner sensitive to the AMP-activated protein kinase (AMPK) inhibitor compound C. Therefore, a direct effect of metformin on CD8(+) T cells is critical for protection against the inevitable functional exhaustion in the tumor microenvironment.
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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.