ArticleOncotarget2013
A lovastatin-elicited genetic program inhibits M2 macrophage polarization and enhances T cell infiltration into spontaneous mouse mammary tumors.
Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
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- Concurrent application of interferon-gamma and vincristine inhibits tumor growth in an orthotopic neuroblastoma mouse model.Pediatric surgery international · 2023Article
- Lipid metabolism reprogramming in tumor-associated macrophages and implications for therapy.Lipids in health and disease · 2023Review
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- Construction and experimental validation of a signature for predicting prognosis and immune infiltration analysis of glioma based on disulfidptosis-related lncRNAs.Frontiers in immunology · 2023Article
- CDK5RAP3 acts as a tumour suppressor in gastric cancer through the infiltration and polarization of tumour-associated macrophages.Cancer gene therapy · 2023Article
- The cholesterol pathway: impact on immunity and cancer.Trends in immunology · 2022Review
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- Tumor-Associated Macrophages: Combination of Therapies, the Approach to Improve Cancer Treatment.International journal of molecular sciences · 2021Review
- Lipid Metabolism in Tumor-Associated Macrophages.Advances in experimental medicine and biology · 2021Review
- Tumor Associated Macrophages, as the Dominant Immune Cells, Are an Indispensable Target for Immunologically Cold Tumor-Glioma Therapy?Frontiers in cell and developmental biology · 2021Review
- Lactoferrin, a unique molecule with diverse therapeutical and nanotechnological applications.International journal of biological macromolecules · 2020Review
- The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy.Acta pharmaceutica Sinica. B · 2020Review
- Hypoxia-Inducible Factor α Subunits Regulate Tie2-Expressing Macrophages That Influence Tumor Oxygen and Perfusion in Murine Breast Cancer.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- SOD3 induces a HIF-2α-dependent program in endothelial cells that provides a selective signal for tumor infiltration by T cells.Journal for immunotherapy of cancer · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Beyond their ability to inhibit cholesterol biosynthesis, the statins have pleiotropic effects that include anti-inflammatory and immunomodulatory activities. Statins could have clinical utility, alone or in combination with other chemotherapeutics, in the treatment of cancer. The mechanisms that underlie the anti-tumor activity of the statins are nonetheless poorly defined. No studies have analyzed how they alter the tumor-associated leukocyte infiltrate, a central factor that influences tumor stroma and cancer evolution. Here we used HER2/neu transgenic (Tg-neu) mice to analyze the effect of lovastatin (Lov) on the inflammatory reaction of spontaneous mammary tumors. Lov treatment of tumor-bearing Tg-neu mice did not alter growth of established tumors, but significantly reduced the number of new oncogenic lesions in these mice. Moreover, Lov inhibited the growth of newly implanted Tg-neu tumors in immunocompetent but not in immunodeficient mice. We found that Lov enhanced tumor infiltration by effector T cells, and reduced the number of immunosuppressive and pro-angiogenic M2-like tumor-associated macrophages (TAM). Concomitantly, the drug improved the structure and function of the tumor vasculature, measured as enhanced tumor oxygenation and penetration of cytotoxic drugs. Microarray analysis identified a Lov-elicited genetic program in Tg-neu tumors that might explain these effects; we observed Lov-induced downregulation of placental growth factor, which triggers aberrant angiogenesis and M2-like TAM polarization. Our results identify a role for lovastatin in the shaping and re-education of the inflammatory infiltrate in tumors, with functional consequences in angiogenesis and antitumor immunity.
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