By comparing variable gene expression and regulons in different clusters and cell types, we not only identified components and characteristics unique to each GBM subtype but also discovered a potential immunotherapeutic target for GBM, Spleen Focus Forming Virus Proviral Integration Oncogene (SPI1), which is expressed in TAM and essential for macrophage maturation and polarization, and correlated with tumor grades and poor prognosis. Here, SPI1 is linked to glioblastoma.