Sunday, September 21, 2025

Nature: Respiratory Viral Infections Awaken Metastatic Breast Cancer Cells in Lungs

 

#18,880

While most people consider influenza and (now) COVID to be a relatively minor, self-limiting, infections - and vaccine uptake for both have fallen - we continue to see evidence of their often devastating extrapulmonary impact. 

BMC Neurology: Long-term Neurological and Cognitive Impact of COVID-19: A Systematic Review and Meta-analysis in over 4 Million Patients

Risk of Cardiovascular Events After Influenza: A Population-based Self Controlled Case Series Study


While all of this is more than enough to inspire me to get the flu/COVID shot every year -  for anyone desirous of additional motivation - we have a recent (July 2025) report in Nature which suggests that respiratory infections can activate dormant cancers (at least, in mice). 

The abstract from the study, and an NIH press release, follow.  I'll have a bit more after the break.

Article
Open access
Published: 30 July 2025
Respiratory viral infections awaken metastatic breast cancer cells in lungs

Abstract

Breast cancer is the second most common cancer globally, with most deaths caused by metastatic disease, often following long periods of clinical dormancy1. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCCs) is crucial for addressing metastatic progression. Infections caused by respiratory viruses such as influenza and SARS-CoV-2 trigger both local and systemic inflammation2,3. 

Here we demonstrate, in mice, that influenza and SARS-CoV-2 infections 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. We show that DCCs impair lung T cell activation and that CD4+ T cells sustain the pulmonary metastatic burden after the influenza infection by inhibiting CD8+ T cell activation and cytotoxicity. Crucially, these experimental findings align with human observational data. 

Analyses of cancer survivors from the UK Biobank (all cancers) and Flatiron Health (breast cancer) databases reveal that SARS-CoV-2 infection substantially increases the risk of cancer-related mortality and lung metastasis compared with uninfected cancer survivors. 

These discoveries underscore the huge impact of respiratory viral infections on metastatic cancer resurgence, offering new insights into the connection between infectious diseases and cancer metastasis.
        (Continue . . . )


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.




Respiratory viruses could awaken dormant cancer cells in the lungs.

CI Photos / Shutterstock

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.

We are coming off one of the worst flu seasons in more than a decade (see
MMWR: Influenza-Associated Hospitalizations During a High Severity Season (United States, 2024–25)).

 

While we can't predict what this fall/winter respiratory season will bring, Dr. Ian Mackay has reported repeatedly on Australia's high-impact flu season the past few months (see A Flunami in July).

Which is why, sometime in the next couple of weeks,  I'll roll up my sleeve to get my 20th seasonal flu shot in as many years.

I recognize it probably only provides my age group with 30%-40% protection.
 
But given the long list of things that can go wrong during or following flu infection, I'll take whatever advantage I can get. 
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