Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Respiratory viral infections awaken metastatic breast cancer cells in lungs

Shi B. Chia, Bryan Johnson, Junxiao Hu, Felipe Valença-Pereira, Marc Chadeau‐Hyam, Fernando Guntoro, Hugh Montgomery, Meher P. Boorgula, Varsha Sreekanth, Andrew Goodspeed, Bennett Davenport, Marco De Dominici, Vadym Zaberezhnyy, Wolfgang E Schleicher, Dexiang Gao, Andreia N. Cadar, Lucia Petriz-Otaño, Michael Papanicolaou, Afshin Beheshti, Stephen B. Baylin, Joseph W. Guarnieri, Douglas C. Wallace, James C. Costello, Jenna M. Bartley, Thomas E. Morrison, Roel Vermeulen, Julio A. Aguirre‐Ghiso, Mercedes Rincón, James DeGregori

Nature · 2025

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Summary

This study reveals that respiratory viral infections (influenza and SARS-CoV-2) disrupt the dormancy of disseminated breast cancer cells in the lung through interleukin-6-dependent mechanisms, triggering rapid proliferation and metastatic expansion within weeks. The mechanism involves impaired lung T cell activation, with CD4+ T cells paradoxically sustaining metastatic burden by inhibiting CD8+ T cell cytotoxicity. These experimental findings are supported by large human observational databases showing that SARS-CoV-2 infection substantially increases cancer-related mortality and lung metastasis risk in breast cancer survivors.

UK applicability

The findings have direct relevance to UK cancer care and survivorship, particularly given the widespread SARS-CoV-2 exposure in the UK population. UK Biobank data were explicitly analysed in this study, making the results directly applicable to UK cancer survivors and informing clinical guidance on infection monitoring and management in this vulnerable population.

Key measures

Dormant disseminated cancer cell (DCC) phenotype transition; interleukin-6 levels; carcinoma cell expansion kinetics; CD4+ and CD8+ T cell activation and cytotoxicity; cancer-related mortality risk; lung metastasis incidence in infected versus uninfected cancer survivors

Outcomes reported

The study demonstrated that influenza and SARS-CoV-2 infections cause dormant breast cancer cells in the lung to lose their quiescent phenotype and proliferate, expanding into metastatic lesions within two weeks in a mouse model. Human observational data from UK Biobank and Flatiron Health databases showed that SARS-CoV-2 infection substantially increased cancer-related mortality and lung metastasis risk in cancer survivors.

Theme
Nutrition & health
Subject
Antimicrobial resistance
Study type
Research
Study design
Mixed methods: experimental (mouse model) with human observational cohort validation
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s41586-025-09332-0
Catalogue ID
BFmou2m94m-xwppca

Topic tags

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