The MEOX1-PAX1 axis coordinately regulates tumor cell malignancy and Treg differentiation in glioblastoma

The immunosuppressive tumor microenvironment (TME) in glioblastoma (GBM) remains a significant therapeutic challenge. This study identified the MEOX1-PAX1 axis as a novel signaling pathway that drives tumor malignancy and fosters immunosuppression. Functional analysis in GBM cells revealed that the transcription factor MEOX1 enhances proliferation, migration, and invasion while suppressing apoptosis, with these effects mediated by its repression of the tumor suppressor PAX1. Notably, beyond its intrinsic cellular role, PAX1 expression in GBM cells strongly influences CD4+ T cell differentiation: overexpression of PAX1 inhibited, while its knockdown promoted, the development of immunosuppressive regulatory T cells (Tregs). This study uncovers the MEOX1-PAX1 axis as a key regulator of GBM progression, promoting both tumor aggressiveness and the creation of an immunosuppressive TME by facilitating Treg differentiation. Targeting this axis offers a promising dual-targeted therapeutic approach for GBM.