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Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
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Glioma‑associated microglia and macrophages as a potential target for mTOR inhibition in glioblastoma

Pia S Zeiner1, Michael Schulz2, Jana Schomber1

  • 1Dr. Senckenberg Institute of Neurooncology, University Hospital, Goethe University Frankfurt, D‑60596 Frankfurt, Germany.

Molecular Medicine Reports
|October 10, 2025
PubMed

Insights

Targeting mTOR signaling in glioma-associated microglia/macrophages (GAM) reduces glioblastoma cell proliferation and promotes inflammation. This suggests mTOR inhibition in GAM is a potential therapeutic strategy for glioblastoma.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Glioma-associated microglia/macrophages (GAM) are the main immune cells in glioblastoma (GB).
  • Both GB cells and GAM show increased mTOR signaling.
  • Targeting mTOR in GAM could impact GB progression.

Purpose of the Study:

  • To investigate the effects of pharmacological mTOR inhibition (mTORi) specifically on GAM.
  • To analyze mTORi's impact on GAM signal transduction, growth, and viability.
  • To explore the potential of mTORi as a novel glioblastoma treatment strategy.

Main Methods:

  • Utilized immortalized microglia cell lines for in vitro analysis.
  • Performed whole transcriptome and cytokine profiling of GAM.
  • Investigated mTORi effects in a co-culture model with GB cells using rapamycin/torin2 and temozolomide.

Main Results:

  • mTOR inhibition significantly reduced GAM proliferation and oxygen consumption.
  • mTORi treatment induced a pro-inflammatory phenotype in microglia.
  • Rapamycin and torin2 demonstrated significant effects on GAM functions.

Conclusions:

  • mTOR signaling is crucial for GAM biology.
  • Targeting mTOR specifically in GAM warrants further investigation for glioblastoma therapy.
  • mTORi presents a potential novel therapeutic avenue for glioblastoma treatment.
Keywords:
gliomamTORmicrogliarapamycintumor microenvironment

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