The resveratrol analogue, HS‑1793, enhances the effects of radiation therapy through the induction of anti‑tumor immunity in mammary tumor growth

2020 
Radiotherapy can induce the infiltration of immune suppressive cells which are involved in promoting tumor progression and recurrence. A number of natural products with immunomodulating abilities have been gaining attention as complementary cancer treatments. This attention is partly due to therapeutic strategies which have proven to be ineffective as a result of tumorinduced immunosuppressive cells found in the tumor microenvironment. The present study investigated whether HS1793, a resveratrol analogue, can enhance the antitumor effects by inhibiting lymphocyte damage and immune suppression by regulatory T cells (Tregs) and tumorassociated macrophages (TAMs), during radiation therapy. FM3A cells were used to determine the role of HS1793 in the radiationinduced tumor immunity of murine breast cancer. HS1793 treatment with radiation significantly increased lymphocyte proliferation with concanavalin A (Con A) stimulation and reduced the DNA damage of lymphocytes in irradiated tumorbearing mice. The administration of HS1793 also decreased the number of Tregs, and reduced interleukin (IL)10 and transforming growth factor (TGF)beta secretion in irradiated tumorbearing mice. In addition, HS1793 treatment inhibited CD206+ TAM infiltration in tumor tissue when compared to the controls or irradiation alone. Mechanistically, HS1793 suppressed tumor growth via the activation of effector T cells in irradiated mice. On the whole, the findings of the present study reveal that HS1793 treatment improves the outcome of radiation therapy by enhancing antitumor immunity. Indeed, HS1793 appears to be a good therapeutic candidate for use in combination with radiotherapy in breast cancer.
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