2026-04-24 インペリアル・カレッジ・ロンドン（ICL）
＜関連情報＞
- https://www.imperial.ac.uk/news/articles/medicine/2026/mice-with-respiratory-infections-could-offer-insights-to-help-stop-cancer-spreading/
- https://www.pnas.org/doi/10.1073/pnas.2412919123
呼吸器ウイルス感染時に誘導されるI型インターフェロンは肺転移の開始を阻害する Type I interferons induced upon respiratory viral infection impair lung metastatic initiation
Ana Farias, Victoria L. Bridgeman, Felipe S. Rodrigues, +6 , and Cecilia Johansson
Proceedings of the National Sciences Published:April 17, 2026
DOI:https://doi.org/10.1073/pnas.2412919123
Significance
The lungs are a metastatic site for cancers such as breast cancer. In addition, the lungs are constantly exposed to viruses, such as coronavirus, respiratory syncytial virus (RSV), and influenza virus. Thus, breast cancer and respiratory virus infection are likely to co-occur, but their interplay remains unclear. We show that type I interferons (IFNs), induced upon viral infection impair metastatic seeding of experimental lung metastases. This occurs via IFNs acting on lung epithelial and endothelial cells, which become less supportive of early tumor cell colonization and proliferation. These findings indicate that viral infections and type I IFNs can alter the lung environment and impair metastatic initiation, which could be explored to improve future cancer treatments.
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.
