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Immunol."],"abstract":"<jats:p>\n                    Inadequate sustained immune activation and tumor recurrence are major limitations of radiotherapy (RT), sustained and targeted activation of the tumor microenvironment can overcome this obstacle. Here, by two models of a primary rat breast cancer and cell co-culture, we demonstrated that valproic acid (VPA) and its derivative (HPTA) are effective immune activators for RT to inhibit tumor growth by inducing myeloid-derived macrophages and polarizing them toward the M1 phenotype, thus elevate the expression of cytokines such as IL-12, IL-6, IFN-\u03b3 and TNF-\u03b1 during the early stage of the combination treatment. Meanwhile, activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells increased, angiogenesis of tumors is inhibited, and the vasculature becomes sparse. Furthermore, it was suggested that VPA\/HPTA can enhance the effects of RT\n                    <jats:italic>via<\/jats:italic>\n                    macrophage-mediated and macrophage-CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell-mediated anti-tumor immunity. The combination of VPA\/HPTA and RT treatment slowed the growth of tumors and prolong the anti-tumor effect by continuously maintaining the activated immune response. These are promising findings for the development of new effective, low-cost concurrent cancer therapy.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.646384","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T01:37:22Z","timestamp":1620783442000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Valproic Acid-Like Compounds Enhance and Prolong the Radiotherapy Effect on Breast Cancer by Activating and Maintaining Anti-Tumor Immune 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