Figure 1. Heterogeneity of the glioblastoma immune microenvironment and potential therapeutic targets.

Within glioblastoma tumors reside ontogenically distinct, immunoregulatory macrophages (Sall1⁺ tumor microglia, Sall1^- monocyte-derived macrophages), immunosuppressive Treg (eg CCR8⁺) and dysfunctional T-cell populations (CTLA-4/PD-1^hi). Not much is known about intratumoral DC subsets, although distinct DC populations are found in other brain regions, such as the dura mater (Van Hove et al., 2019). Glioblastoma also affects the phenotype of classical monocytes (Cl. Monocyte) in the periphery, which acquire an immunosuppressive (MDSC-like?) phenotype. Notably, the genetic make-up of the cancer cells (blue rectangle) and potentially also of the glioblastoma stem cells, affect the immune composition of the tumor, with for example a higher presence of lymphocytes in TCGA-MES tumors. Several potential therapeutic targets (CSF1R, SIRPa, CCR8, PD-1, CTLA-4), either already tested in the clinic or promising for the future, are highlighted.