Study details and key findings

For the study, researchers used a unique mouse model of metastatic breast cancer, which included dormant disseminated cancer cells (DCCs), or cells that break off from a primary tumor and spread to other organs. The mice overexpressed a gene related to the human gene HER2, which produces a protein that causes breast cancer cells to reproduce rapidly.

According to James DeGregori, a biochemistry professor at the University of Colorado School of Medicine and one of the study's senior authors, the mouse model was designed to show what human patients with breast cancer may experience over several years or even decades.

After exposing the mice to either influenza viruses or SARS-CoV-2, the COVID-19 virus, the researchers found that the metastatic burden in the mice increased significantly, between 100-fold and 1000-fold. The researchers also found that viral infection caused dormant cancer cells to evolve into a previously unrecognized hybrid state, which suggests that the infection somehow promoted the activation of cancer cells.

Through a molecular analysis, the researchers found that the dormant DCCs were reactivated by interleukin-6 (IL-6), an inflammatory protein released by immune cells in response to injuries or infection. According to STAT, other studies have linked inflammation, as well as IL-6 specifically, to the formation of metastatic lesions.

In addition, the researchers found that CD4 cells, a type of immune T cells, seemed to suppress anti-tumor activity after viral infection, which made it harder to eliminate cancer cells.

"Instead of the immune system actively eliminating the cancer cells, it protects them from immune elimination," DeGregori said. "We need to better understand this mechanism of immune suppression so that perhaps we can reverse it and allow the immune system to better control the cancer."

Commentary

According to some outside researchers, the study's findings are valid, but there are still several limitations.

For example, Grace Bushnell, a biomedical engineer at the University of Minnesota, said the study's model did not match the clinical reality for most patients with breast cancer since they usually undergo surgery to remove their tumors. This did not happen with the mice in the study, so the findings represent a different situation.

Separately, Sophia Orbach, a biomedical engineer at Rowan University, said that the study's findings should not be applied to all breast cancer cells since the mice experiments were specifically done using HER2-positive cells, which only account for roughly 30% of all breast cancer cases.

However, John Alcorn, an immunology professor at the University of Pittsburgh, said that the study has significant implications since it demonstrates that acute infections can also severely impact an individual's health.

"It's an exciting link between acute infections and a reactivation of these dormant cells that can lead to cancer progression," Alcorn said. "Something that we once thought of as a two-week problem really has far-reaching effects beyond that."

Bushnell also noted that the study's findings add to growing evidence that environmental conditions, like inflammation, can contribute to cancer metastasis.

"The seed of the cancer cell has to find a soil that is permissive to it growing," Bushnell said, referencing Stephen Paget's 1889 metastasis theory. "It's not really just as simple as, 'we know exactly what wakes up cancer cells in specific organs at specific times.'"