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

Weili Ma, Maria Cecília Oliveira-Nunes, Ke Xu, Andrew Kossenkov, Benjamin C Reiner, Richard C Crist, James Hayden, Qing Chen

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish
Article number2632
Pages (from-to)2632
JournalNature Communications
Volume14
Issue number1
StatePublished - May 6 2023
Externally publishedYes

Keywords

  • Humans
  • Interferon Type I/metabolism
  • Astrocytes/metabolism
  • Chemokine CCL2/metabolism
  • Myeloid Cells/metabolism
  • Brain Neoplasms/pathology
  • Receptors, CCR2/metabolism
  • Tumor Microenvironment

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