2. Academic Validation
  3. TLR7 modulates glioblastoma progression through PI3K/AKT/mTOR pathway and immune microenvironment remodeling

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

  • Ir J Med Sci. 2025 Dec 13. doi: 10.1007/s11845-025-04208-8.
Liwen Guo 1,  Xianlei Zhou 2,  Zhi Zhang 3,  Xuemei Zhang 4 5
Affiliations

Affiliations

  • 1 College of Life Sciences, North China University of Science and Technology, Tangshan, China.
  • 2 School of Public Health, North China University of Science and Technology, Tangshan, China.
  • 3 Tangshan Gongren Hospital, North China University of Science and Technology, Tangshan, China. [email protected].
  • 4 College of Life Sciences, North China University of Science and Technology, Tangshan, China. [email protected].
  • 5 School of Public Health, North China University of Science and Technology, Tangshan, China. [email protected].
PMID: 41389249 DOI: 10.1007/s11845-025-04208-8
Abstract

Background: Glioblastoma (GBM) is an aggressive brain tumor, necessitating the identification of new therapeutic targets. Toll-like Receptor 7 (TLR7), a key component of innate immunity, influences oncological processes, but its role in GBM is unclear. This study investigates the impact of TLR7 overexpression on GBM and its underlying mechanisms.

Methods: Glioblastoma cell lines (U87 and U251) were transfected with a pcDNA-TLR7 plasmid to induce overexpression, verified by qRT-PCR. Proliferation was assessed using CCK-8 and colony formation assays. Migration and invasion were evaluated via Transwell and wound healing assays. Activation of the PI3K/Akt/mTOR signaling pathway was analyzed by Western blotting. Macrophage polarization was studied by exposing M0 macrophages to the TLR7 Agonist R837, followed by qRT-PCR and cytokine quantification.

Results: TLR7 was successfully overexpressed in U87 and U251 cells. TLR7 overexpression significantly reduced GBM cell proliferation, colony formation, migration, and invasion. It suppressed the PI3K/Akt/mTOR signaling pathway. In the tumor microenvironment, TLR7 promoted M1 macrophage polarization, increasing M1 markers and pro-inflammatory cytokines while suppressing M2 markers.

Conclusion: TLR7 suppresses glioblastoma by inhibiting cell progression via the PI3K/Akt/mTOR signaling pathway and promoting an anti-tumoral immune microenvironment. These findings suggest the potential of TLR7 as a promising therapeutic target for GBM.

Keywords

GBM; Macrophage polarization; PI3K/AKT/mTOR signaling pathway; TLR7; Therapeutic target.

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