Due to extensive infiltration of immunosuppressive immune cells (e.g., TAMs, MDSCs, neutrophils, and Tregs), GBM is featured as a “cold” tumor with relatively low cytotoxic T-cells. Targeting the GBM-immune symbiosis (e.g., GBM-TAM, GBM-MDSC, GBM-neutrophil, GBM-T cell, and CSC-Treg) shifts the “cold” TME to “hot”, thus inhibiting tumor growth and synergizing with immunotherapies (e.g., ICI therapies) in GBM. Abbreviations: GBM, glioblastoma; ICI, immune checkpoint inhibitor; MDSC, myeloid-derived suppressor cell; TAM, tumor-associated macrophage and microglia; TME, tumor microenvironment.