Some cancer cells don't die; they go quiet, like seeds lying dormant in the soil. These "sleeper cells," scattered throughout the body, can stay inactive for years. But when the body faces a respiratory virus like influenza or SARS-CoV-2, the resulting inflammation (both locally in the lungs and systemically throughout the body) acts like an alarm clock. It jolts these silent cells awake, especially in the lungs, giving them a chance to grow and spread.
A recently published study in Nature reveals that such viral wake-up calls can turn a dormant threat into a deadly one, increasing the risk of metastasis and cancer-related death. Researchers from the University of Colorado Cancer Center have now demonstrated that in mice, viral infections reawaken breast cancer cells, and within days, these cells begin to multiply. Experiments showed that after two weeks, they've built full-blown metastatic strongholds in the lungs.
During the COVID-19 pandemic, researchers posed a chilling question: Could respiratory viruses like the flu or SARS-CoV-2 act as hidden accomplices in cancer's comeback?
To find out, they turned to mice engineered with dormant breast cancer cells tucked away in their lungs, cells that had gone quiet. Once infected with either flu or SARS-CoV-2, the mice showed a jaw-dropping response: those quiet cancer cells roared back to life, multiplying more than 100-fold. Within days, the lungs transformed into battlegrounds of aggressive tumor growth.
The findings were so dramatic that the team wondered whether similar patterns could be found in human data. While the mouse models focused solely on breast cancer, the implications of this discovery may ripple far wider, suggesting that viral inflammation could be a universal trigger for metastatic awakening.
"The findings are likely applicable to other types of cancer," explains James DeGregori from the University of Colorado Cancer Center, "Dormant cancer cells are like the embers left in an abandoned campfire, and respiratory viruses are like a strong wind that reignites the flames."
Researchers analyzed health data from the UK and the US to study cancer patients who had COVID-19 in 2020, before vaccines were available. They found that people with past cancer diagnoses (5–10 years ago) who tested positive for COVID-19 had a higher risk of dying from cancer. This increased risk was most pronounced within a year after the infection.
"The odds ratio for death from cancer was substantial for the first year (2020), which means they were much more likely to die of their cancer if they got COVID," added Roel Vermeulen from Utrecht University, "The extent of this increased risk is almost unheard of in epidemiology for cancer. It's a significant effect."
The increased cancer risk seen in people after COVID-19 closely matched what was seen in the mice experiments, where dormant cancer cells rapidly grew after infection. Further analysis of breast cancer patient data showed that COVID-19 significantly raised the chances of the cancer spreading to the lungs.
"What our data suggest is that if you are a cancer patient who has these dormant cells, you may end up living a normal life and dying with these dormant cells, instead of dying because those dormant cells awaken," DeGregori said. "But if you get a respiratory virus like influenza or COVID, your chance of dying from those dormant cells awakening is much greater."
The researchers are cautious to note that their observational findings are based on data gathered in human patients before COVID vaccines were available. It is hypothesized vaccination could lower the risk of COVID waking dormant cancer cells because vaccinated individuals tend to react to an infection with a better regulated immune response.
This points to the key culprit in the discovery – interleukin-6 (IL6), a fiery molecule released during inflammation. It is a cytokine that acts like a biochemical alarm bell, flipping the switch in cancer cells from dormancy to aggressive growth.
In severe COVID cases, doctors may use a special antibody to block IL6. By stopping IL6's signal, they can reduce the body's overreaction and help improve survival.
Although more research is needed before changing medical guidelines, the study uncovered biological pathways that existing FDA-approved drugs can target. These treatments could potentially lower the risk of cancer spreading in survivors who get viral lung infections like the flu or COVID-19.
Given the dramatic results of their initial research, scientists are now delving deeper into how viral infections like COVID-19 or the flu reawaken dormant cancer cells. They aim to uncover the biological mechanisms behind this process, explore how it might be blocked, and investigate whether the immune system can be harnessed to eliminate these reactivated cells.
Their future studies will also address critical follow-up questions: Does the type of cancer a person had influence their risk after infection, or are all cancer survivors vulnerable? Is the threat limited to lung metastasis, or could it extend to other organs such as the brain and bones? And significantly, does vaccination against respiratory viruses reduce this risk?
These inquiries could pave the way for new strategies to protect cancer survivors from metastatic resurgence triggered by viral illness.
"Respiratory viral infections are forever a part of our lives, so we need to understand the longer-term consequences of these infections," DeGregori adds.
The findings are published in the Journal Nature.
