Metastatic breast cancer cells awakened by lung infections

A new study recently published on Nature shows that viral infections such influenza or SARS-CoV-2 can disrupt the quiescence of dormant disseminated breast cancer cells in the lungs of mice, leading to metastatic progression.

Viral respiratory infections are typically associated with pulmonary inflammation; noticing that death rates from cancer rose in the first two years of the COVID-19 pandemic, authors hypothesized that pulmonary viral infections increase cancer deaths by triggering the development of metastases from dormant disseminated cancer cells (DCC). By using the MMTV-ErbB2/Neu/Her2 mouse model of breast cancer metastatic dormancy, authors demonstrated that influenza and SARS-CoV-2 infections, by triggering both local and systemic inflammation, lead to loss of the pro-dormancy phenotype in breast DCCs in the lung, causing DCC proliferation within days of infection and a massive expansion of carcinoma cells into metastatic lesions within two weeks. These phenotypic transitions and expansions are interleukin-6 dependent; moreover, DCCs impair lung T cell activation. As authors underscore, these mice data align with human observational data: UK Biobank analyses show that cancer survivors had increased cancer mortality after SARS-CoV-2 infection, with a risk peaking in the months after infection, paralleling mouse models showing greater than 100-fold DCC expansion into metastatic lesions within two weeks. «Our studies reveal how respiratory virus infections can increase cancer recurrence risk and underscore the need for public health and clinical strategies to mitigate the increased risk of metastatic progression associated with SARS-CoV2 and other respiratory virus infections», authors conclude.