ArticleScientific reports2022
Metformin sensitizes leukemic cells to cytotoxic lymphocytes by increasing expression of intercellular adhesion molecule-1 (ICAM-1).
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Paracetamol and Metformin Reduce NK-Cell Susceptibility in MCF-7 Breast Cancer Cells in Association with Enrichment of Immune-Evasive CD44International journal of molecular sciences · 2026Article
- Deciphering the Anti-Tumor Mechanisms of Metformin Through Reprogramming of the Tumor Microenvironment.Cells · 2026Review
- Review
- Role of cancer cell-derived exosomal glycoproteins in macrophage polarization.Molecular biology reports · 2025Review
- Is the MAPK ERK5 the nexus from FAO to NK cell-mediated metastasis immune surveillance?Frontiers in immunology · 2025Review
- Resveratrol contributes to NK cell-mediated breast cancer cytotoxicity by upregulating ULBP2 through miR-17-5p downmodulation and activation of MINK1/JNK/c-Jun signaling.Frontiers in immunology · 2025Article
- Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells.MedComm · 2024Article
- Receptors and Host Factors for Enterovirus Infection: Implications for Cancer Therapy.Cancers · 2024Review
- Generation of non-genetically modified, CAR-like, NK cells.Journal for immunotherapy of cancer · 2024Article
- Recent Advances in Immune-Based Therapies for Acute Myeloid Leukemia.Blood cancer discovery · 2024Review
- Double-negative T cells utilize a TNFα-JAK1-ICAM-1 cytotoxic axis against acute myeloid leukemia.Blood advances · 2024Article
- Serum Levels of Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Molecule 1 as Biomarkers to Predict Radiotherapy Sensitivity in Cervical Cancer.Geburtshilfe und Frauenheilkunde · 2024Article
- STAT3 in acute myeloid leukemia facilitates natural killer cell-mediated surveillance.Frontiers in immunology · 2024Article
- SUMOylation inhibitor TAK-981 (subasumstat) synergizes with 5-azacytidine in preclinical models of acute myeloid leukemia.Haematologica · 2024Article
- Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.Frontiers in pharmacology · 2024Review
- Dynamic Changes in miRNA Expression during the Generation of Expanded and Activated NK Cells.International journal of molecular sciences · 2023Article
- Metformin promotes antitumor activity of NK cells via overexpression of miRNA-150 and miRNA-155.American journal of translational research · 2023Article
- NK cells in peripheral blood carry trogocytosed tumor antigens from solid cancer cells.Frontiers in immunology · 2023Article
- Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy.Medicina (Kaunas, Lithuania) · 2022Review
- Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The anti-diabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of anti-apoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.
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