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

Meiyan Qi, Yun Xia, Yanjun Wu, Zhuo Zhang, Xinyu Wang, Liying Lu, Cheng Dai, Yanan Song, Keying Xu, Weiwei Ji and Lixing Zhan ()
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Meiyan Qi: Chinese Academy of Sciences
Yun Xia: Huazhong University of Science and Technology
Yanjun Wu: Chinese Academy of Sciences
Zhuo Zhang: East China University of Science and Technology
Xinyu Wang: Chinese Academy of Sciences
Liying Lu: Chinese Academy of Sciences
Cheng Dai: Chinese Academy of Sciences
Yanan Song: Chinese Academy of Sciences
Keying Xu: Chinese Academy of Sciences
Weiwei Ji: Chinese Academy of Sciences
Lixing Zhan: Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-28438-x

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