Here, we used single-cell RNA-Seq (scRNA-Seq) analysis followed by functional studies to show that TAM-derived LGMN promotes tumor progression and immunosuppression by dually targeting GBM cells and macrophages through a mechanism of activating the glycogen synthase kinase 3β (GSK3β)/signal transducer and activator of transcription 3 (STAT3) and integrin αv/protein kinase B (AKT)/NF-κB p65 (p65) pathways, respectively. Here, AKT1 is linked to glioblastoma.