Respiratory Viruses Like Flu Or COVID Could Cause ‘Sleeping’ Cancer Cells To Wake Up

In A Nutshell

Respiratory viruses like flu and COVID-19 may awaken dormant breast cancer cells in the lungs — at least in mice.
Mice infected with these viruses showed a 100–1,000x increase in sleeping cancer cells within two weeks.
A key immune protein called IL-6 triggers the reactivation, while CD4+ T cells help the cancer persist.
Human data shows cancer survivors with COVID-19 faced higher risks of death and lung metastases — but the findings show correlation, not causation.

AURORA, Colo. — Common respiratory infections like the flu and COVID-19 might jolt dormant cancer cells back to life in survivors, causing them to multiply and spread in the lungs. This new research offers a potential explanation for why cancer deaths rose during the COVID-19 pandemic, suggesting it wasn’t solely due to delayed screenings and treatments.

In a lab study published in Nature, scientists found that when mice with dormant breast cancer cells were infected with the flu, the number of those sleeping cancer cells in their lungs increased by 100 to 1,000 times within just two weeks. A similar dramatic effect was observed when the mice were infected with a version of the coronavirus that causes COVID-19.

Most people think of cancer as either present or absent, but the reality is more complex. After successful cancer treatment, tiny clusters of cancer cells (sometimes just single cells) can remain in a dormant state for years or even decades. These sleeping cells stay alive but don’t grow or spread, and this dormancy is why some cancer patients experience a recurrence long after their initial treatment.

Why Respiratory Infections Trigger Cancer Cell Growth

The research team from the University of Colorado Anschutz Medical Campus used genetically modified mice that develop breast cancer similar to humans. These mice naturally develop dormant cancer cells in their lungs that can remain inactive for up to a year, which mimics what happens in human cancer survivors.

When researchers infected these mice with the influenza A virus, the dormant cancer cells began dividing within three days. By 15 days post-infection, the number of cancer cells had increased dramatically, and they remained elevated even months later.

The key to this awakening is a protein called interleukin-6, or IL-6. When viruses infect the lungs, they trigger inflammation, and as part of this response, lung cells produce IL-6. This protein acts as a wake-up call for the dormant cancer cells. Scientists proved IL-6’s central role by using mice that were genetically engineered to lack the protein. When these mice caught the flu, their dormant cancer cells stayed asleep. The viral infection proceeded normally, but without IL-6, the cancer cells remained dormant.

The process unfolds in two distinct phases. First, the viral infection and IL-6 production cause the cells to awaken and multiply rapidly. After the acute infection subsides and IL-6 levels drop, immune cells called CD4+ T cells take over to maintain the expanded cancer cell population. Instead of eliminating the awakened cancer cells, these immune cells actually protect them by suppressing other immune cells, called CD8+ T cells, that would normally hunt down and destroy the cancer.

Human Data Supports Lab Findings

Human data from two large databases supports these laboratory findings. A study of the UK Biobank, which tracked nearly 5,000 cancer survivors who had been in remission for at least five years before the pandemic, found that those who tested positive for COVID-19 had a higher risk of death.

COVID-positive cancer survivors were 4.5 times more likely to die from any cause compared to those who tested negative.
Even after excluding deaths directly caused by COVID-19, the positive group still had a 2.56 times higher mortality rate.
Most concerning was cancer-specific mortality, where COVID-positive survivors were 1.85 times more likely to die from cancer.

A separate analysis of the Flatiron Health database, which contains medical records from nearly 37,000 women with breast cancer, revealed that those who contracted COVID-19 after their cancer diagnosis had a 44% increased risk of developing lung metastases compared to women who didn’t get the virus. The increased risk of cancer death was greatest in the months immediately following the COVID-19 infection and decreased over time, a trend that mirrors what researchers observed in mice.

Cancer Survivors Need Better Protection from Respiratory Viruses

These findings provide a potential explanation for a puzzling observation from the early pandemic: cancer death rates rose significantly in 2020 and 2021, beyond what could be fully explained by COVID-19 deaths or delays in cancer care. Millions of COVID-19 infections may have awakened dormant cancer cells in survivors, leading to increased recurrences and deaths.

The research opens up new possibilities for protecting cancer survivors from infection-triggered recurrences. For example, some treatments for severe COVID-19, such as drugs that block IL-6 signaling, might be able to prevent the virus-induced reawakening of cancer cells. However, the timing of such a treatment would be critical to prevent the cancer from waking up without interfering with the body’s ability to fight the infection.

For the millions of Americans with a history of cancer, this study suggests that the threat of recurrence extends far beyond what oncologists traditionally monitor. The invisible battle between dormant cancer cells and the immune system continues long after the final treatment, and respiratory viruses have emerged as an unexpected threat in that ongoing fight.

Paper Summary

Methodology

The researchers used two main approaches. First, they conducted experiments on genetically modified mice with dormant breast cancer cells in their lungs, infecting them with either influenza A virus or a mouse-adapted version of SARS-CoV-2. They also used mice lacking the IL-6 protein to understand its role in the process. Second, they analyzed large human datasets—the UK Biobank (4,837 cancer survivors) and the Flatiron Health database (36,845 breast cancer patients)—to look for correlations between COVID-19 infection and cancer outcomes.

Results

Infected mice showed a dramatic increase in dormant cancer cells in their lungs, with numbers rising by 100 to 1,000 times within 15 days of infection. This effect was dependent on the IL-6 protein; mice without IL-6 did not experience this cancer cell awakening. Human data from the UK Biobank showed that COVID-19-positive cancer survivors had 4.5 times higher all-cause mortality and 1.85 times higher cancer-specific mortality compared to COVID-negative survivors. The Flatiron Health data indicated a 44% increased risk of developing lung metastases among breast cancer patients who contracted COVID-19.

Limitations

The mouse studies used models that may not perfectly reflect human cancer biology, and the human observational data shows correlation, not causation. The UK Biobank analysis was limited to tests done before December 2020 and may have missed some cases, while the Flatiron Health database lacked a COVID-negative control group, which could underestimate the effect. The study also focused mainly on breast cancer, so the findings might not apply to all cancer types.