EIF4A3/ALKBH5 axis promotes meningioma cell growth, invasion, and resistance to CD8+ T cell-mediated cytotoxicity by inducing M2 polarization.

Meningioma (MM) is the most prevalent primary tumor in the central nervous system. This study sought to unveil the mechanism by which Alkylation repair homolog protein 5 (ALKBH5) regulates tumor-associated macrophages (TAMs) M2-like polarization and modulates the resistance of MM cells to CD8+ T cell-mediated cytotoxicity. The data showed that ALKBH5 upregulation was positively correlated with M2-like TAM polarization. ALKBH5 knockdown suppressed TAM M2-like polarization and the aggressive phenotypes of MM cells, thus inhibiting tumor growth. Additionally, EIF4A3 knockdown attenuated TAM M2-like polarization, suppressed invasive phenotypes of MM cells, and reduced MM cell resistance to CD8+ T cell-mediated cytotoxicity in vitro by inhibiting ALKBH5. ALKBH5 promoted TGF-β1 expression in an m6A-dependent manner. TGF-β1 reversed the ALKBH5 knockdown-mediated effects. In summary, EIF4A3-mediated upregulation of ALKBH5 elevated the malignant phenotypes of MM cells and their resistance to CD8+ T cell-mediated cytotoxicity in vitro by facilitating TAM M2-like polarization and TGF-β1 secretion.