Type I interferons induced upon respiratory viral infection impair lung metastatic initiation
Author(s)
Type
Journal Article
Abstract
Metastatic breast cancer accounts for 7% of cancer-related deaths, with the lungs being a common site of cancer spread. In parallel, lower respiratory tract infections, including those caused by respiratory syncytial virus (RSV), remain a common cause of morbidity and mortality worldwide. Acute viral respiratory infections induce marked changes in the lung. However, how these changes influence metastasis initiation and cancer progression remains unclear. Using breast cancer and other cancer cell types in an experimental lung metastasis model, we show that RSV infection impairs tumor cell seeding and early growth in the lung, resulting in fewer metastatic nodules. We demonstrate that restriction of metastatic spread is due to alterations in the lung environment mediated by RSV-induced type I interferons (IFNs). Consistent with this idea, intranasal administration of recombinant IFN-α is sufficient to recapitulate the anti-metastatic effect of RSV infection. Using single cell RNA sequencing supported by in vivo and ex vivo validation, we show that IFN-α influences interactions between epithelial/endothelial cells and cancer cells. Furthermore, both RSV infection and IFN-α administration trigger marked local and systemic upregulation of Galectin-9, an IFN-inducible protein associated with acute respiratory infection in humans. Treatment of cancer cells with Galectin-9 alone is sufficient to restrict metastatic seeding. Altogether, our results suggest that type I IFNs induced by respiratory virus infection render the lungs less permissive to cancer cell seeding and consequently interfere with the ability of tumor cells to successfully initiate metastatic colonization.
Date Issued
2026-04-21
Date Acceptance
2026-02-19
Citation
Proceedings of the National Academy of Sciences, 2026, 123 (16)
ISSN
0027-8424
Publisher
National Academy of Sciences
Journal / Book Title
Proceedings of the National Academy of Sciences
Volume
123
Issue
16
Copyright Statement
© 2026 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41996163
Subjects
epithelial cells
immune cells
lung metastases
virus infection
Animals
Lung Neoplasms
Female
Humans
Interferon Type I
Respiratory Syncytial Virus Infections
Mice
Interferon-alpha
Cell Line, Tumor
Respiratory Syncytial Viruses
Respiratory Tract Infections
Neoplasm Metastasis
Lung
Breast Neoplasms
Publication Status
Published
Coverage Spatial
United States
Article Number
e2412919123
Date Publish Online
2026-04-17