A new study in Nature has shown that respiratory viral infections such as influenza and COVID-19 can awaken dormant breast cancer cells in the lungs, increasing the likelihood of relapse and metastasis.
Breast cancer cells can remain inactive for years after initial treatment, hiding as disseminated cancer cells (DCCs) until conditions in the body trigger them to grow again. Using mouse models of HER2+ breast cancer, researchers found that influenza A virus infection caused dormant cells in the lungs to reactivate dramatically—up to 1,000-fold within two weeks. The key driver was inflammation, particularly the signaling molecule interleukin-6 (IL-6), which pushed the cancer cells from a resting “mesenchymal” state into a hybrid, rapidly growing form.
The study revealed a two-step process: first, IL-6 stimulates the reawakening and expansion of dormant cancer cells; second, CD4+ T cells interfere with CD8+ immune cells, preventing them from destroying these reactivated cells.
Experiments using SARS-CoV-2 (the virus responsible for COVID-19) showed similar effects. Infected mice developed more proliferating cancer cells, and human data supported these findings. Analysis of the UK Biobank showed cancer survivors who tested positive for COVID-19 had a higher risk of death, even excluding deaths directly caused by COVID-19.
Data from the Flatiron Health Database also suggested women with breast cancer who contracted COVID-19 might face an increased risk of metastasis to the lungs, although the effect was modest and not statistically definitive.
Overall, the study highlights how viral infections disrupt the tumor microenvironment, creating conditions that allow dormant cancer cells to awaken and spread. The findings stress the importance of close monitoring of breast cancer patients after viral illnesses and point to IL-6 signaling as a potential therapeutic target to reduce relapse risk.
