Non-Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment.


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,
Journal: Nat Commun;2023May06; 14 (1) 2632. doi:10.1038/s41467-023-38252-8
Year: 2023
PubMed: PMID: 37149684 (Go to PubMed)