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

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 tumor-induced immunosuppressive cells found in the tumor microenvironment. The present study investigated whether HS-1793, a resveratrol analogue, can enhance the anti-tumor effects by inhibiting lymphocyte damage and immune suppression by regulatory T cells (Tregs) and tumor-associated macrophages (TAMs), during radiation therapy. FM3A cells were used to determine the role of HS-1793 in the radiation-induced tumor immunity of murine breast cancer. HS-1793 treatment with radiation significantly increased lymphocyte proliferation with concanavalin A (Con A) stimulation and reduced the DNA damage of lymphocytes in irradiated tumor-bearing mice. The administration of HS-1793 also decreased the number of Tregs, and reduced interleukin (IL)-10 and transforming growth factor (TGF)-β secretion in irradiated tumor-bearing mice. In addition, HS-1793 treatment inhibited CD206(+) TAM infiltration in tumor tissue when compared to the controls or irradiation alone. Mechanistically, HS-1793 suppressed tumor growth via the activation of effector T cells in irradiated mice. On the whole, the findings of the present study reveal that HS-1793 treatment improves the outcome of radiation therapy by enhancing antitumor immunity. Indeed, HS-1793 appears to be a good therapeutic candidate for use in combination with radiotherapy in breast cancer.