蒲公英通过CUEDC2调节肿瘤细胞与TAMs的交互作用重塑三阴乳腺癌免疫微环境

三阴乳腺癌（TNBC）的局部复发及远处转移率较高，预后差，缺乏有效治疗靶点和药物，是乳腺癌研究的焦点。本项目前期研究发现：TNBC和肿瘤相关巨噬细胞（TAMs）存在交互作用，CUEDC2能调控参与该作用的关键分子及肿瘤免疫微环境。中药蒲公英能降低CUEDC2表达，抑制TNBC恶性表型，下调免疫抑制分子，促TAMs向M1极化，激发肿瘤内部炎症反应，协同提高PD-1单抗的生长抑制作用。本项目拟阐明CUEDC2在TNBC和TAMs交互作用中的调控靶点，明确蒲公英是否通过CUEDC2重塑免疫微环境发挥抗肿瘤效应。本项目密切结合中医药传统理论与现代科学研究方法，选择蒲公英所入肝经的循行部位（乳腺）肿瘤及其微环境为研究对象，为蒲公英治疗TNBC提供科学依据，给“蒲公英为治疗乳疾要药”的理论进行科学支撑，蒲公英调节肿瘤微环境提高免疫疗法效果为TNBC的治疗提供新思路，具有重要的理论意义和应用价值。

Triple-negative breast cancer (TNBC) has a high rate of local recurrence and distant metastasis, poor prognosis, and lack of effective therapeutic targets and drugs. It becomes the hot topic of breast cancer research. Our previous study showed that TNBC bidirectional interacts with tumor-associated macrophages (TAMs), and CUEDC2 can regulate the key molecules involved interaction process, as well as the tumor immune microenvironment. Dandelion is a Traditional Chinese Medicine that can reduce the expression of CUEDC2, inhibit the malignant phenotype of TNBC, down-regulate immunosuppressive molecules, promote the polarization of TAMs to M1, thus stimulating the inflammatory response in tumor, and synergistically improving the efficacy of anti-PD-1 monoclonal antibody on growth inhibition of TNBC cells. This project intends to clarify the key steps and targets of CUEDC2 regulating the interaction between TNBC and TAMs, and to determine whether dandelion exerts an anti-tumor effect through remodeling of tumor immune microenvironment by targeting CUEDC2. In this project, it has a tight combination between the theory of Traditional Chinese medicine and modern research technology. We chose breast cancer as the subject to study as dandelion distributes to live channel according to the theory of channel tropism theories. The results of present project will provide scientific basis for dandelion as an effective herb drug to treat TNBC, offer new ideas for the treatment of TNBC, and give a scientific support for the theory of “dandelion is an important herb for the treatment of breast disease”. The effects of regulating tumor microenvironment to improve the efficacy of immunotherapy by dandelion, will provides new ideas for the treatment of TNBC. Therefore, the present study has important theoretical significance and applicational value.