Respiratory viruses may trigger dormant cancers

August 19, 2025

Respiratory viruses may trigger dormant cancers

At a Glance

A study in mice showed how common respiratory viruses may awaken dormant cancer cells.
The findings suggest these viruses can pose additional risks for people with a history of cancer.

Abstract illustration of lungs in distress.

Respiratory viruses could awaken dormant cancer cells in the lungs.

Cancer cells can break away from their original tumors and travel to different parts of the body. These disseminated cancer cells (DCCs) can then grow into new tumors. This process is called metastasis. DCCs can stay dormant for years or decades before awakening and developing into tumors, even long after the original tumor is removed. What causes the cells to awaken has been unknown.

Studies have shown that cancer metastasis can be triggered by inflammation. Infection by respiratory viruses, such as influenza and SARS-CoV-2, often causes inflammation. A research team led by Dr. James DeGregori at the University of Colorado Anschutz Medical Campus set out to test whether respiratory virus infections might cause DCCs to awaken. To do this, they used mouse models of breast cancer to study the effects of influenza and SARS-CoV-2 infection on DCCs and metastasis in the lungs. The study appeared in Nature on July 30, 2025.

Before infection, the mice’s lungs contained only a small number of isolated DCCs. Within three days of infection with influenza virus, the lungs had a striking increase in number of DCCs. This number continued to grow over the course of two weeks and remained elevated even 9 months after infection. The increase in DCCs was accompanied by a decline in the share of DCCs that were in a dormant state. Similar effects were seen in mice infected with SARS-CoV-2.

Further experiments showed that the virus-induced awakening of DCCs required the inflammatory signaling molecule IL-6. Mice that couldn’t produce IL-6 had much less DCC growth and a greater share of dormant DCCs in their lungs after influenza infection. Moreover, organoids formed from the mice’s mammary glands grew significantly when treated with IL-6.

The team noted that DCCs tended to cluster near immune cells called CD4⁺ T cells. Depleting CD4⁺ T cells reduced the number of DCCs that were still awake one month after infection. It also increased the number of CD8⁺ T cells, which kill cancer and virus-infected cells, in the lungs. CD8⁺ T cells in CD4⁺ T cell-depleted mice were more effective at killing breast cancer cells. This suggests that CD4⁺ T cells aid awakened DCCs by suppressing CD8⁺ T cell activity.

The team next looked at the association between SARS-CoV-2 infection and cancer progression and mortality in electronic health records. They examined data from the UK Biobank on almost 5,000 people who had a prior cancer diagnosis and were inferred to be in remission. Among this population, a positive test for SARS-CoV-2 nearly doubled the risk of death from cancer. In a separate dataset of more than 36,000 women with breast cancer, having COVID-19 increased the risk of metastasis to the lungs by about 40%.

The findings suggest how respiratory virus infections may contribute to the risk of cancer recurrence and metastasis. They also point to potential targets for interventions that could reduce this risk.

“Dormant cancer cells are like the embers left in an abandoned campfire, and respiratory viruses are like a strong wind that reignites the flames,” DeGregori explains.

—by Brian Doctrow, Ph.D.

References

Chia SB, Johnson BJ, Hu J, Valença-Pereira F, Chadeau-Hyam M, Guntoro F, Montgomery H, Boorgula MP, Sreekanth V, Goodspeed A, Davenport B, De Dominici M, Zaberezhnyy V, Schleicher WE, Gao D, Cadar AN, Petriz-Otaño L, Papanicolaou M, Beheshti A, Baylin SB, Guarnieri JW, Wallace DC, Costello JC, Bartley JM, Morrison TE, Vermeulen R, Aguirre-Ghiso JA, Rincon M, DeGregori J. Nature. 2025 Jul 30. doi: 10.1038/s41586-025-09332-0. Online ahead of print. PMID: 40739350.

Funding

NIH’s National Cancer Institute (NCI), National Institute on Aging (NIA), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of General Medical Sciences (NIGMS), and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); US Department of Veterans Affairs; Kay Sutherland and Monika Weber Research Fund; University of Colorado School of Medicine; Samuel Waxman Cancer Research Foundation; Cancer League of Colorado; UK Medical Research Council; UK National Institute for Health Research; Cancer Research Institute; US Department of Defense; Bill & Melinda Gates Foundation.

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