二甲双胍通过下调抑制性细胞和免疫检查点分子，同时激活乳腺癌中的保护性免疫反应，发挥抗肿瘤作用。
Metformin plays an antitumor role by downregulating inhibitory cells and immune checkpoint molecules while activating protective immune responses in breast cancer.
发表日期：2023 Mar 28
作者：
Haoran Jiang, Huandan Suo, Liwei Gao, Ye Liu, Bo Chen, Shilong Lu, Feng Jin, Yu Cao
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要：
本研究旨在测试二甲双胍治疗对携带4T1乳腺癌细胞BALB/c小鼠乳腺癌结果的影响。通过流式细胞术和ELISA评估脾脏免疫细胞和肿瘤微环境的变化，比较小鼠的存活率和肿瘤大小。我们的研究结果表明，二甲双胍延长了小鼠的存活时间。治疗二甲双胍能明显降低小鼠脾脏中M2型巨噬细胞（F4 / 80 + CD206 +）的数量。治疗还抑制了单核细胞源性抑制细胞（M-MDSCs，CD11b + Gr-1 +）和调节性T细胞（Tregs，CD4 + CD25 + Foxp3 +）。治疗结果导致IFN-γ水平升高，IL-10水平降低。治疗后，T细胞上的免疫检查点分子PD-1受到抑制。二甲双胍增强了肿瘤微环境中的局部抗肿瘤活性，我们的数据支持该药物成为乳腺癌治疗评估的候选药物。版权所有© 2023 Elsevier B.V. All rights reserved.
This study seeks to test the effect of metformin treatment on the outcomes of breast cancer in BALB/c mice bearing 4 T1 breast cancer cells. The survival rate and tumor size of mice were compared, as well as evaluation of the changes of immune cells in spleens and the microenvironment of tumors using flow cytometry and ELISA. Our results demonstrate that metformin prolongs mouse survival. A significant decrease in M2-like macrophages (F4/80+CD206+) was found in mice spleen treated with metformin. The treatment also inhibited monocytic myeloid-derived suppressor cells (M-MDSCs, CD11b+Gr-1+) and regulatory T cells (Tregs, CD4+CD25+Foxp3+). Metformin treatment resulted in an increase in the level of IFN-γ and a decrease in IL-10. Expression of the immune checkpoint molecule PD-1 on T cells was inhibited following treatment. Metformin enhances local antitumor activity in the tumor microenvironment, and our data supports the drug as a candidate for evaluation in the treatment of breast cancer.Copyright © 2023 Elsevier B.V. All rights reserved.