Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment.
Abstract
Cancer metastasis to the brain is a significant clinical problem. Metastasis is the consequence of favorable interactions between invaded cancer cells and the microenvironment. Here, we demonstrate that cancer-activated astrocytes create a sustained low-level activated type I interferon (IFN) microenvironment in brain metastatic lesions. We further confirm that the IFN response in astrocytes facilitates brain metastasis. Mechanistically, IFN signaling in astrocytes activates C-C Motif Chemokine Ligand 2 (CCL2) production, which further increases the recruitment of monocytic myeloid cells. The correlation between CCL2 and monocytic myeloid cells is confirmed in clinical brain metastasis samples. Lastly, genetically or pharmacologically inhibiting C-C Motif Chemokine Receptor 2 (CCR2) reduces brain metastases. Our study clarifies a pro-metastatic effect of type I IFN in the brain even though IFN response has been considered to have anti-tumor effects. Moreover, this work expands our understandings on the interactions between cancer-activated astrocytes and immune cells in brain metastasis.
Authors: | Ma W, Oliveira-Nunes MC, Xu K, Kossenkov A, Reiner BC, Crist RC, Hayden J, Chen Q, |
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Journal: | Nat Commun;2023May06; 14 (1) 2632. doi:10.1038/s41467-023-38252-8 |
Year: | 2023 |
PubMed: | PMID: 37149684 (Go to PubMed) |