Figure 1.

Glioblastoma Tumor Microenvironment: The GBM TME is complex, with a series of unique features, interactions, and components—the ECM, with glycoproteins, proteoglycans, and glycosaminoglycans (e.g., HA), has an important role in creating a barrier between the GBM TME and the normal tissue, promoting invasiveness; the immune cells (GAMs, TANs, monocytes, tumor-infiltrating lymphocytes), neuronal cells, glial cells, and glioma stem cells; chemokines, hormones, enzymes, EVs, and cell-communicating factors like VEGF, EGFR, and mediators like glutamate, with all of them being involved in creating an hypoxic and immunosuppressive TME that promotes tumoral progression and therapy resistance. The blood–brain barrier is also important in modulating the GBM TME components and can limit tissue drug availability, playing an important role in therapy resistance.