TLR7 modulates glioblastoma progression through PI3K/AKT/mTOR pathway and immune microenvironment remodeling

Area of Science:

• Neuro-oncology
• Immunology
• Molecular Biology

Background:

• Glioblastoma (GBM) is a highly aggressive brain tumor with limited therapeutic options.
• Toll-like receptor 7 (TLR7), part of the innate immune system, has an unclear role in GBM pathogenesis.
• Identifying novel therapeutic targets is crucial for improving GBM treatment outcomes.

Purpose of the Study:

• To investigate the effect of Toll-like receptor 7 (TLR7) overexpression on glioblastoma (GBM) progression.
• To elucidate the underlying molecular mechanisms, including signaling pathways and immune microenvironment modulation.
• To assess the therapeutic potential of targeting TLR7 in GBM.

Main Methods:

• Overexpression of TLR7 in human glioblastoma cell lines (U87, U251) using plasmid transfection.
• Assessment of cell proliferation, migration, and invasion using CCK-8, colony formation, Transwell, and wound healing assays.
• Analysis of PI3K/AKT/mTOR pathway activation via Western blotting and macrophage polarization using qRT-PCR and cytokine analysis.

Main Results:

• Successful overexpression of TLR7 confirmed by qRT-PCR.
• TLR7 overexpression significantly inhibited GBM cell proliferation, colony formation, migration, and invasion.
• TLR7 suppressed the PI3K/AKT/mTOR signaling pathway and promoted M1 macrophage polarization, enhancing anti-tumoral immunity.

Conclusions:

• TLR7 acts as a suppressor of glioblastoma by inhibiting cell progression through the PI3K/AKT/mTOR pathway.
• TLR7 promotes an anti-tumoral immune microenvironment by modulating macrophage polarization.
• TLR7 represents a promising therapeutic target for glioblastoma treatment.