HMGB1 and neoplasm: Extracellular HMGB1 has been reported to activate its receptors on GB cells through the downstream signaling pathway [e.g., NF-kB, IFN regulatory factor-3 (IRF3) and phosphoinositide 3-kinase (PI3K)] to produce a functional immune response, such as activation of tumor-associated dendritic cells (TADC), CD8+ T cells and macrophages [21, 22].