Glioma‑associated microglia and macrophages as a potential target for mTOR inhibition in glioblastoma.

Glioma‑associated microglia/macrophages (GAM) constitute the predominant immune cell population in glioblastoma (GB). Both GB cells and GAM exhibit upregulated mTOR signaling. The present study aimed to investigate the effects of pharmacological mTOR inhibition (mTORi) specifically on GAM. The effects of mTORi on signal transduction, cell growth and viability were analyzed in immortalized microglia cell lines. Additionally, a comprehensive analysis of the GAM phenotype was conducted, including whole transcriptome analyses and cytokine profiling. Effects were investigated in a tumor cell/GAM co‑culture model under mTORi with rapamycin or torin2 or treatment with temozolomide, the standard chemotherapy agent for patients with GB. In the in vitro model, mTORi had significant effects on central biological functions of GAM, resulting in reduced proliferation and oxygen consumption. Additionally, treatment with mTORi induced a pro‑inflammatory phenotype in microglia cell lines. These findings demonstrate the relevance of mTOR signaling on GAM biology. Moreover, they provide rationales for therapeutic interventions targeting mTOR signaling specifically in GAM as a potential novel treatment strategy.