肿瘤微环境在肿瘤的发生、发展以及免疫逃逸过程中起关键作用。本课题组前期研究发现IL-33通过诱导肿瘤组织中浸润未成熟DC（imDC）和Treg细胞并参与乳腺癌的发展，而这种作用可能跟Notch信号通路的活化有关。本项目拟结合细胞和动物水平，利用knockdown和过表达Jagged1-Notch家族、ST2基因敲除鼠和抗体阻断IL-33的作用等干预措施，使用免疫荧光、免疫印迹、Luminex芯片、染色质免疫共沉淀等实验方法，研究Jagged1-Notch信号通路的活化对IL-33的调控及肿瘤微环境的影响，包括诱导imDC富集、Treg生成及活化内皮细胞，这些作用机制又进一步促进肿瘤局部Notch家族的表达，从而形成正反馈调节，导致乳腺癌的发展和转移；最后使用临床样本研究Notch信号通路的活化与IL-33、DC及Treg产生的相关性，并可望为临床乳腺癌的治疗干预提供新的研究策略和理论依据。

The tumor microenvironment is crucial for tumor immune escape.Our previous findings have found that Interleukin-33 (IL-33) is involved in breast cancer by inducing infiltration of immature dendritic cells (imDC) and regulatory T cells (Treg), and this role of IL-33 maybe caused by the activatation of Notch signaling pathway. In this study, we would knockdown and overexpressed Notch family, use ST2-/- mice model and the blockade of IL-33 to study the activation of Jagged1-Notch signaling pathway on the regulation of IL-33 and the role of immune cells in tumor microenvironment by using immunofluorescence, western blot, Luminex chip, Chromatin immunoprecipitation et al. Then we want demonstrate the mechanism of imDC gaccumulation, Treg generatation, angiogenesis and activation of Notch signaling pathway on endothelial cells, by which local IL-33 forms positive feedback regulation and would further promote the development and metastasis of breast cancer. Lastly, to confirm our conclusion above by analyzing DC and Treg in breast tumor tissues, and the IL-33 in serum from patients with mammary carcinoma. Our program will provide more scientific evidences for establishing new therapeutic target for human tumor treatment especially mammary carcinoma.