ArticleJournal of neuroinflammation2014
The mTOR kinase inhibitors polarize glioma-activated microglia to express a M1 phenotype.
Article in Journal of neuroinflammation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Systematic Review on Tumor Microenvironment in Glial Neoplasm: From Understanding Pathogenesis to Future Therapeutic Perspectives.International journal of molecular sciences · 2022Pooled it
- Review
- Glioma‑associated microglia and macrophages as a potential target for mTOR inhibition in glioblastoma.Molecular medicine reports · 2025Article
- mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025Review
- Mechanistic Insights into the Anti-Glioma Effects of Exosome-Like Nanoparticles Derived fromInternational journal of nanomedicine · 2025Article
- Tissue-Resident Macrophages in Cancer: Friend or Foe?Cancer medicine · 2024Review
- Lipid metabolic rewiring in glioma‑associated microglia/macrophages (Review).International journal of molecular medicine · 2024Review
- The Interplay between Glioblastoma Cells and Tumor Microenvironment: New Perspectives for Early Diagnosis and Targeted Cancer Therapy.Brain sciences · 2024Review
- mTOR Inhibition Is Effective against Growth, Survival and Migration, but Not against Microglia Activation in Preclinical Glioma Models.International journal of molecular sciences · 2023Article
- Exosome-based nanoimmunotherapy targeting TAMs, a promising strategy for glioma.Cell death & disease · 2023Review
- Recruitment mechanisms and therapeutic implications of tumor-associated macrophages in the glioma microenvironment.Frontiers in immunology · 2023Review
- Single unit analysis and wide-field imaging reveal alterations in excitatory and inhibitory neurons in glioma.Brain : a journal of neurology · 2022Article
- Inhibition of mTOR in bovine monocyte derived macrophages and dendritic cells provides a potential mechanism for postpartum immune dysfunction in dairy cows.Scientific reports · 2022Article
- CMTM6 knockdown prevents glioma progression by inactivating the mTOR pathway.Annals of translational medicine · 2022Article
- The Pivotal Immunoregulatory Functions of Microglia and Macrophages in Glioma Pathogenesis and Therapy.Journal of oncology · 2022Review
- The Role of Micro RNAs in Regulating PI3K/AKT Signaling Pathways in Glioblastoma.Iranian journal of pathology · 2022Review
- The Coordination of mTOR Signaling and Non-Coding RNA in Regulating Epileptic Neuroinflammation.Frontiers in immunology · 2022Review
- The effects of painless nerve growth factor on human microglia polarization.Frontiers in cellular neuroscience · 2022Article
- Review
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreased activation of mammalian target of rapamycin (mTOR) is observed in numerous human cancers. Recent studies on the glioma kinome have identified several deregulated pathways that converge and activate mTOR. The available evidence on the role of microglia in CNS cancers would suggest a dual role, a tumoricidal role and -on the contrary- a role favoring tumor growth.
methodsIn the present paper, we have compared the effects of μM concentrations of rapamycin (RAPA) and its analog, RAD001 (RAD), on activated microglia; the latter was obtained by exposing cells to conditioned medium harvested either from inflammatory activated glioma cells (LI-CM) or from glioma cells kept under basal conditions (C-CM).
resultsHere we show that the inhibition of mTOR polarizes glioma-activated microglial cells towards the M1 phenotype, with cytotoxic activities, preventing the induction of the M2 status that promotes tumor growth. In fact RAPA and RAD significantly increased iNOS expression and activity, while on the same time significantly reducing IL-10 gene expression induced by C-CM, thus suggesting that the drugs prevent the acquisition of a M2 phenotype in response to glioma factors promoting a classic M1 activation. Similar results were obtained using the conditioned media obtained after glioma stimulation with LPS-IFNγ (LI-CM), which was found to induce a mixture of M1 and M2a/b polarization phenotypes. In these conditions, the inhibition of mTOR led to a significant up-regulation of iNOS, and in parallel to the down-regulation of both ARG and IL-10 gene expression.
conclusionsThese data suggest that mTOR inhibition may prevent glioma induced M2 polarization of microglial cells and increase their cytotoxic potential, possibly resulting in antitumor actions.
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