乳腺癌是女性中发病率位于第一位的恶性肿瘤，乳腺癌的转移是导致患者死亡的主要原因，其中肺脏是乳腺癌转移的主要器官，因此，研究乳腺癌肺转移的区域免疫特性具有重要的意义。本项目拟利用小鼠乳腺癌4T1建立肺转移模型，筛选肺脏高转移的亚克隆细胞系。在此基础上，研究乳腺癌肺转移过程中肺、脾脏和引流淋巴结中主要免疫细胞亚群的动态变化，通过选择性的删除特定的细胞亚群等方法研究对乳腺癌肺转移起关键作用的细胞亚群。另外，研究在这些关键细胞亚群上表达的主要免疫共抑制分子PD-1、LAG3和TIGIT等在乳腺癌转移过程中作用，并且首次利用课题组建立的镜像噬菌体展示技术筛选针对这些共抑制分子的D肽拮抗肽，探讨这些新型拮抗肽干预乳腺癌肺转移的作用效果和机制，本研究将为乳腺癌转移的机制和治疗方法研究提供重要的理论基础。

Breast cancer is the first suffered cancer type among women. Metastasis of breast cancer is the main cause of the lethality. The main organ to the metastasis is lung. Therefore, it is very important to study the regional immune properties of lung metastasis of breast cancer. In this project, The lung metastasis model will be established in mice by using 4T1 cell line, the sub-clone of lung metastasis will be screened. Based on these, the dynamic changes of the main immune cell population in lung, spleen and draining lymphonode will be studied during the lung metastasis, the key population which lead to the metastasis will be found out. The role of the putative co-inhibitory molecules such as PD-1, LAG3, and TIGIT expressed on these cells will be also studied. The mirror-imaged phage display peptide library biopanning technique will be introduced to find blocking peptides consist of D-amino acids targeting these co-inhibitory molecules. The theraputic effects and mechanism of these novel blocking peptides will be studied. This project will provide important data for the mechanism study and therapy of breast cancer metastasis.