文献类型：期刊文献

英文题名：Lin28B-high breast cancer cells promote immune suppression in the lung pre-metastatic niche via exosomes and support cancer progression

作者：Qi, Meiyan[1];Xia, Yun[2];Wu, Yanjun[1];Zhang, Zhuo[3];Wang, Xinyu[1];Lu, Liying[1];Dai, Cheng[1];Song, Yanan[1];Xu, Keying[1];Ji, Weiwei[1];Zhan, Lixing[1]

机构：[1]Chinese Acad Sci, Univ Chinese Acad Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai Inst Nutr & Hlth,Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China;[2]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Thyroid & Breast Surg, 1095 Jiefang Ave, Wuhan 430030, Peoples R China;[3]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ct, State Key Lab Bioreactor Engn, 130 Mei Long Rd, Shanghai 200237, Peoples R China

年份：2022

卷号：13

期号：1

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000757370100016)】；

基金：We thank Lin Qiu, Yifan Bu, Feng Zhao, Zhonghui Weng, Aimin Huang, Cheng Wang, Kai Wang, Konglun Pan, and Hui Zhu at the Institute of Nutrition and Health core facilities for technical support. This study was supported by the National Key Research and Development Program of China (2020YFA0112300, 2017YFC1600100 to L.Z.), Program of EnShi TuJia & Miao Autonomous Prefecture Bureau of Scientific & Technological Affair (L.Z.), and National Natural Science Foundation of China (82173007 and 81872369 to L.Z., 81301855 to M.Q.).

语种：英文

摘要：The formation of pre-metastatic niche is a key step in the metastatic burden. The pluripotent factor Lin28B is frequently expressed in breast tumors and is particularly upregulated in the triple negative breast cancer subtype. Here, we demonstrate that Lin28B promotes lung metastasis of breast cancer by building an immune-suppressive pre-metastatic niche. Lin28B enables neutrophil recruitment and N2 conversion. The N2 neutrophils are then essential for immune suppression in pre-metastatic lung by PD-L2 up-regulation and a dysregulated cytokine milieu. We also identify that breast cancer-released exosomes with low let-7s are a prerequisite for Lin28B-induced immune suppression. Moreover, Lin28B-induced breast cancer stem cells are the main sources of low-let-7s exosomes. Clinical data further verify that high Lin28B and low let-7s in tumors are both indicators for poor prognosis and lung metastasis in breast cancer patients. Together, these data reveal a mechanism by which Lin28B directs the formation of an immune-suppressive pre-metastatic niche. The establishment of a pre-metastatic niche is a key step preceding metastasis formation. Here the authors show that tumor-intrinsic Lin28B, a RNA-binding protein, has an essential role in the formation of an immune-suppressive pre-metastatic niche, promoting lung metastasis of breast cancer.