The resveratrol analogue, HS-1793, enhances the effects of radiation therapy through the induction of anti-tumor immunity in mammary tumor growth
The resveratrol analogue, HS-1793, enhances the effects of radiation therapy through the induction of anti-tumor immunity in mammary tumor growth
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DOI：
10.3892/ijo.2020.5017
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发表时间：
2020-06-01
影响因子：
5.2
通讯作者：
Jeong, Min Ho
中科院分区：
文献类型：
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作者：
Kim, Joong Sun;Jeong, Soo Kyung;Jeong, Min Ho
放射治疗可诱导免疫抑制细胞浸润，参与促进肿瘤进展和复发。许多具有免疫调节能力的天然产品作为补充癌症治疗方法已经受到关注。这种关注部分是由于治疗策略已被证明是无效的，因为在肿瘤微环境中发现了肿瘤诱导的免疫抑制细胞。本研究探讨了白藜芦醇类似物HS-1793在放射治疗中是否可以通过抑制淋巴细胞损伤和调节性T细胞（TCFs）和肿瘤相关巨噬细胞（TAMs）的免疫抑制来增强抗肿瘤作用。FM 3A细胞用于确定HS-1793在放射诱导的小鼠乳腺癌肿瘤免疫中的作用。HS-1793处理与辐射显着增加伴刀豆球蛋白A（Con A）刺激的淋巴细胞增殖，并减少辐射荷瘤小鼠淋巴细胞的DNA损伤。HS-1793的给药还减少了经辐照的荷瘤小鼠中的T细胞的数量，并减少了白细胞介素（IL）-10和TGF-β的分泌。此外，HS-1793治疗抑制CD 206（+）TAM浸润肿瘤组织相比，对照组或单独照射。从机制上讲，HS-1793通过激活辐射小鼠中的效应T细胞来抑制肿瘤生长。总的来说，本研究的结果表明，HS-1793治疗通过增强抗肿瘤免疫改善了放射治疗的结果。事实上，HS-1793似乎是一个很好的治疗候选人，用于与乳腺癌放疗联合使用。
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)-beta 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.