In conclusion, we demonstrated that CpG ODN107+ irradiation induces autophagic cell death via the TLR9-ERK-mTOR signaling pathway in glioma cells (Fig. 8), thus, further elucidating the mechanism by which CpG ODN107+ irradiation induces autophagy and providing new insights into the radiosensitizing effects of CpG ODN107 in tumor cells. Here, TLR9 is linked to central nervous system cancer.