TLR9 and central nervous system cancer: For example, the activation of TLR9 promotes apoptosis in the glioma.325 In hepatocellular carcinoma (HCC), activation of TLR3 can downregulate anti-apoptotic proteins such as Bcl-xL and survivin, and synergistically augment TRAIL-induced apoptosis, thereby promoting cancer cell death.356 Stimulation of TLR3 in tumor cells derived from human head and neck cancer has also been found to downregulate the anti-apoptotic protein survivin.357 Additionally, both TLR4 and TLR7 have been implicated in the direct induction of cellular apoptosis.