Irradiation Enhances Abscopal Anti-Tumor Effects of Antigen-Specific Immunotherapy through Regulating Tumor Microenvironment Han-Wei Lin, M.A.1, and Yu-Li Chen, M.D., Ph.D.2* 1Graduate Institute of Oncology, 2Department of Obstetrics and Gynecology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan *Corresponding Author
Background: Ionizing radiation therapy (RT) is a well-established method of eradicating locally advanced tumors. Here we examined whether local RT enhanced the potency of an antigen-specific DNA vaccine, and investigated the possible underlying mechanism. Methods: Using the HPV16 E6/E7+ syngeneic TC-1 tumor, we evaluated the combination of CTGF/E7 vaccination with local irradiation with regards to synergistic antigen-specific immunity and anti-tumor effects. Results: Tumor-bearing mice treated with local RT (6 Gy twice weekly) and CTGF/E7 DNA vaccination exhibited dramatically increased numbers of E7-specific CD8+ cytotoxic T-cell precursors, higher titers of anti-E7 Abs, and significantly reduced tumor size. The combination of local RT and CTGF/E7 vaccination also elicited abscopal effects on non-irradiated local subcutaneous and distant pulmonary metastatic tumors. Local irradiation induced the expression of high-mobility group box 1 protein (HMGB-1) in apoptotic tumor cells and stimulated dendritic cell (DC) maturation, consequently inducing antigen-specific immune responses. Additionally, local irradiation eventually increased the effector-to-suppressor cell ratio in the tumor microenvironment. Conclusion: Overall, local irradiation enhanced the antigen-specific immunity and anti-tumor effects on local and distant metastatic tumors generated by an antigen-specific DNA vaccine. These findings suggest that the combination of irradiation with antigen-specific immunotherapy is a promising new clinical strategy for cancer therapy.
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