Functional assays demonstrated that DOK3 knockdown reduced CD163 expression and attenuated glioma cell invasiveness, supporting its role in promoting M2 polarization and tumor aggressiveness.<h4>Conclusion</h4>This integrative analysis identifies DOK3 as a pivotal regulator of M2 macrophage polarization and a driver of glioblastoma progression. Here, DOK3 is linked to central nervous system cancer.