Using the PDGFb-driven replication-competent avian sarcoma-leukosis virus/ tumor virus A (RCAS/Tv-a) murine high-grade glioma model injected into GPNMB-KO and control mice, we demonstrate that host-derived GPNMB is of detrimental importance for glioma growth and immune cell composition. Here, PDGFB is linked to central nervous system cancer.