Conclusions: Our findings revealed the role of the novel HDAC7-H3K27ac-SOX8/JUN-LGALS3-ITGB1 axis in maintaining the crosstalk between MES GBM and M2 MDM, highlighting that HDAC7 and LGALS3 may serve as potential prognostic biomarkers and therapeutic targets in GBM. The gene discussed is SOX8; the disease is glioblastoma.