Respiratory infections like Covid or the flu can “wake up” dormant cancer cells in the lungs

The results “are really quite dramatic.” James DeGregori, a cancer biologist at the University of Colorado School of Medicine in Aurora and one of the study’s authors, explains the concern: “Respiratory virus infections didn’t just wake up cells”; they also caused them to proliferate, or multiply, “in enormous numbers.”

The research, now published in Nature , used mice, but the results corroborate what has been found in humans: data from thousands of people show that infection with the SARS-CoV-2 coronavirus is associated with a nearly twofold increase in cancer-related deaths, which may help explain why cancer death rates rose at the start of the Covid-19 pandemic.

Researchers have identified dormant cancer cells, separate from the original tumor, hidden in tissues such as bone marrow in people in remission from breast, prostate, and skin cancer, among others. These cells are precursors to metastasis—the spread of cancer to distant organs—and pose a problem even in survivors of these types of cancer.

Scientists have long been trying to figure out what triggers these cells to reawaken. Previous work suggested chronic inflammation, such as that caused by smoking and aging, is the culprit. This idea led DeGregori and his team to wonder whether acute inflammation caused by a respiratory infection could also reactivate dormant cancer cells. To do so, they used genetic engineering techniques to induce breast cancer in mice and seed dormant tumor cells in other tissues, such as the lungs. They then infected the rodents with either the COVID-19 virus or the flu.

Within days, dormant cancer cells in the animals' lungs became active, proliferated, and metastasized. The researchers discovered, however, that it wasn't the respiratory viruses directly causing this effect, but rather IL-6, a key immune system molecule. In mice genetically modified to lack this molecule, the multiplication of dormant cancer cells was much slower.

In addition to the role of IL-6, T cells, also part of the immune system, have also been shown to play an important role in this process, protecting cancer cells from other immune system defenses. "Seeing that these cancer cells were perverting the immune system to protect them rather than eliminate them was quite shocking," says DeGregori.

But there's another relevant fact: this "awakening" of cancer cells didn't last. About two weeks after "waking up," the cells went dormant, leading scientists to conclude that infections don't directly cause cancer, but they do make it more likely that another infection will reactivate the cancer in the future. DeGregori compares the process to repeatedly lighting a fire: "We build flames, and then they go out. But now we have 100 times more embers than we had before."