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Abstract
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 antitumor 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.

Affiliations

Joong Sun Kim  1 , Soo Kyung Jeong  2 , Su Jung Oh  2 , Chang Geun Lee  2 , Yeong Rok Kang  2 , Wol Soon Jo  2 , Min Ho Jeong  3
1 Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju‑si, Jeollanam‑do 58245, Republic of Korea.
2 Department of Research Center, Dong Nam Institute of Radiological and Medical Sciences, Jangan‑eup, Gijang‑gun, Busan 619‑953, Republic of Korea.
3 Department of Microbiology, Dong‑A University College of Medicine, Seo‑gu, Busan 602‑714, Republic of Korea.