SLC10A3 drives glioblastoma progression by remodeling the immunosuppressive microenvironment and promoting M2 macrophage migration

Introduction Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis, limited therapeutic options, and a highly immunosuppressive microenvironment. This study investigated the clinical significance and biological role of SLC10A3 in GBM progression and immune evasion. Methods Bulk transcriptomic data from TCGA and CGGA cohorts were analyzed to assess SLC10A3 expression and prognostic value. Functional enrichment, single-cell RNA sequencing, and cell–cell communication analyses were performed to explore SLC10A3-related pathways and cellular distribution. In vitro and in vivo experiments were conducted to evaluate the effects of SLC10A3 knockdown on GBM malignant phenotypes and macrophage recruitment. Results SLC10A3 was significantly overexpressed in GBM and associated with poor prognosis. Enrichment analyses linked SLC10A3 to PI3K-Akt, NF-κB, HIF-1 signaling, macrophage infiltration, and T-cell suppression. Single-cell analysis showed SLC10A3 enrichment in tumor-associated astrocytes and macrophages, with enhanced astrocyte–macrophage crosstalk through MIF, MDK, and extracellular matrix remodeling pathways. SLC10A3 knockdown inhibited GBM cell proliferation, migration, and invasion, induced cell cycle arrest and apoptosis, reduced M2 macrophage migration, and suppressed xenograft tumor growth. Discussion SLC10A3 may promote GBM aggressiveness and immune evasion by regulating malignant phenotypes and macrophage-associated immunosuppression, suggesting its potential as a therapeutic target for GBM.