Abstract 3674: Local irradiation promotes antitumor immunity and abscopal effect of antigen-specific immunotherapy by enhancing dendritic cell maturation

Abstract

Abstract Background: Ionizing radiation therapy (RT) is a well-established method to eradicate locally advanced tumors. Whether or no local RT can enhance the potency of an antigen-specific DNA vaccine and the possible underlying mechanism were evaluated. Materials and Methods: The number of E7-specific CD8+ cytotoxic T cell precursors and anti-E7 Abs from Tumor-bearing mice treated with local RT (6Gy twice per week) and the CTGF/E7 DNA vaccine were evaluated. Abscopal effects were also monitored. HMGB-1and DC maturation from local irradiation were analyzed by flow cytometry. The ratio of effector-to-suppressor cells in the tumor microenvironment was also investigated. Results: Tumor-bearing mice treated with local RT (6Gy twice per week) and the CTGF/E7 DNA vaccine exhibited a dramatic increase in the number of E7-specific CD8+ cytotoxic T cell precursors, higher titers of anti-E7 Abs, a significant reduction of tumor size, and longer survival. The combination of local RT and the CTGF/E7 vaccine also elicited abscopal effects on non-irradiated local subcutaneous and distant pulmonary metastatic tumors. Local irradiation can induce the expression of HMGB-1 in apoptotic tumor cells and stimulate DC maturation, which results in inducing antigen-specific immune responses. In addition, local irradiation, although inducing Treg cells, can eventually increase a higher ratio of effector-to-suppressor cells in the tumor microenvironment. Conclusions: Local irradiation can enhance the antigen-specific immunity and antitumor effects on local and distant metastatic tumors generated by an antigen-specific DNA vaccine. Irradiation combined with antigen-specific immunotherapy is a potential new strategy for cancer therapy. Citation Format: Ming-Cheng Chang, Jason Chia-Hsien Cheng, Ying-Cheng Chiang. Local irradiation promotes antitumor immunity and abscopal effect of antigen-specific immunotherapy by enhancing dendritic cell maturation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3674. doi:10.1158/1538-7445.AM2017-3674