TLR4 in glioblastoma—when cancer stem cells ignore “danger signals”
The microenvironment of glioblastoma is hostile to both invading and resident cells. Tumor cells in the tumor core are challenged by hypoxia, acidosis and have to resist attacks of invading microglia cells and other invading immune cells (1,2). In their recent paper, Alvarado et al. studied the role of Toll-like receptors (TLR) in glioblastoma cancer stem cells (CSC) and tumor cells without stem cell properties (3). TLRs have a well-established role in the innate immune system: Endogenous molecules liberated from damaged tissue or by pathogen-associated molecular patterns (e.g., lipopolysaccharides) activate TLR receptors during tissue injury or infection (4). This allows the detection of damage and of pathogen associated molecular pattern (“danger signals”) and constitutes a crucial mechanism for activation of the innate immune system and especially dendritic cells.