|Title:||Irradiation Enhances Abscopal Anti-tumor Effects of Antigen-Specific Immunotherapy through Regulating Tumor Microenvironment||Authors:||Chang M.-C.
|Issue Date:||2018||Journal Volume:||26||Journal Issue:||2||Start page/Pages:||404-419||Source:||Molecular Therapy||Abstract:||
Ionizing radiation therapy 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 we investigated the possible underlying mechanism. Using the HPV16 E6/E7+ syngeneic TC-1 tumor, we evaluated the combination of CTGF/E7 vaccination with local irradiation with regard to synergistic antigen-specific immunity and anti-tumor effects. 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. 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. Cheng and colleagues show that TC-1 tumor-bearing mice treated with local irradiation and CTGF/E7 DNA vaccination exhibited dramatically increased numbers of E7-specific CD8+ cytotoxic T cell precursors and significantly reduced tumor size. This combinational strategy also elicited abscopal effects on non-irradiated local subcutaneous and distant pulmonary metastatic tumors. ? 2017 The American Society of Gene and Cell Therapy
|ISSN:||1525-0016||DOI:||10.1016/j.ymthe.2017.11.011||SDG/Keyword:||antibody; DNA vaccine; E7 antibody; high mobility group B1 protein; unclassified drug; cancer vaccine; high mobility group B1 protein; tumor antigen; animal cell; animal experiment; animal model; animal tissue; antibody titer; antigen specificity; antineoplastic activity; apoptosis; Article; blood cell ratio; cancer immunotherapy; cancer radiotherapy; CD4+ T lymphocyte; CD8+ T lymphocyte; cell maturation; controlled study; dendritic cell; drug mechanism; drug potency; effector to supppressor cell ratio; female; immune response; lung metastasis; mouse; nonhuman; protein expression; radiation dose fractionation; regulatory mechanism; treatment duration; tumor microenvironment; tumor volume; whole body radiation; animal; cytotoxicity; disease model; drug screening; genetics; human; immunology; immunotherapy; metabolism; multimodality cancer therapy; neoplasm; pathology; procedures; regulatory T lymphocyte; tumor microenvironment; Animals; Antigens, Neoplasm; Cancer Vaccines; CD8-Positive T-Lymphocytes; Combined Modality Therapy; Cytotoxicity, Immunologic; Dendritic Cells; Disease Models, Animal; HMGB1 Protein; Humans; Immunotherapy; Mice; Neoplasms; T-Lymphocytes, Regulatory; Tumor Microenvironment; Whole-Body Irradiation; Xenograft Model Antitumor Assays
|Appears in Collections:||醫學系|
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