This study uncovers the profound impact of anoikis-mediated changes in the tumor microenvironment (TME) at the single-cell level, finding that BRMS1 promotes M2 polarization in microglia and activates the PI3K/AKT signaling pathway through SPP1/CD44-mediated cell interactions, inhibiting GBM cell apoptosis and promoting proliferation, migration, and invasion, leading to adverse effects on the prognosis and immune therapy response of GBM patients. This evidence concerns the gene CD44 and glioblastoma.