Respiratory viruses can wake up breast cancer cells in lungs

(Press-News.org) JULY 30, 2025—Researchers at the University of Colorado Anschutz Medical Campus, Montefiore Einstein Comprehensive Cancer Center (MECCC), and Utrecht University have found the first direct evidence that common respiratory infections, including COVID-19 and influenza, can awaken dormant breast cancer cells that have spread to the lungs, setting the stage for new metastatic tumors. The findings published today in Nature, obtained in mice, were supported by research showing increases in death and in metastatic lung disease among cancer survivors infected with SARS-CoV-2, the virus that causes COVID-19.

“Our findings indicate that individuals with a history of cancer may benefit from taking precautions against respiratory viruses, such as vaccination when available, and discussing any concerns with their healthcare providers,” said Julio Aguirre-Ghiso, Ph.D., a co-leader of the study and director of MECCC’s Cancer Dormancy Institute, professor of cell biology, of oncology, and of medicine and the Rose C. Falkenstein Chair in Cancer Research at Albert Einstein College of Medicine.

The study was led by senior author and deputy director of CU Cancer Center James DeGregori, Ph.D., and also co-led by Mercedes Rincon, Ph.D., with CU Anschutz, and Roel Vermeulen, Ph.D., of Utrecht University, The Netherlands, and Imperial College London. “This complex and multidisciplinary study truly took a village,” said Dr. DeGregori.

Arousing ‘Sleeper Cells’ in Mice

Prior to the study, some evidence suggested that inflammatory processes can awaken disseminated cancer cells (DCCs)—cells that have broken away from a primary tumor and spread to distant organs, often lying dormant for extended periods. “During the COVID-19 pandemic, anecdotal reports suggested a possible increase in cancer death rates, bolstering the idea that severe inflammation might contribute to arousing dormant DCCs,” said Dr. Aguirre-Ghiso, who also serves as leader of MECCC’s Tumor Microenvironment and Metastasis Research Program.

Researchers tested this hypothesis using Dr. Aguirre-Ghiso’s laboratory’s unique mouse models of metastatic breast cancer, which include dormant DCCs in the lungs and therefore closely resemble a key feature of the disease in humans.

The researchers exposed mice to SARS-CoV-2 or influenza virus. In both cases, the respiratory infections triggered the awakening of dormant DCCs in the lungs, leading to a massive expansion of metastatic cells within days of infection and the appearance of metastatic lesions within two weeks.

“Dormant cancer cells are like the embers left in an abandoned campfire, and respiratory viruses are like a strong wind that reignites the flames,” said Dr. DeGregori.

Molecular analyses revealed that the awakening of dormant DCCs is driven by interleukin-6 (IL-6), a protein that immune cells release in response to infections or injuries. “The identification of IL-6 as a key mediator in arousing DCCs from dormancy suggests that using IL-6 inhibitors or other targeted immunotherapies might prevent or lessen the resurgence of metastasis following viral infection,” said Dr. Aguirre-Ghiso.

Two Population Studies Also Show Risk for People

The COVID-19 pandemic offered a unique opportunity to investigate the effect of respiratory virus infections—in this case from the SARS-CoV-2 virus—on cancer progression. The research team analyzed two large databases and found support for their hypothesis that respiratory infections in cancer patients in remission are linked to cancer metastasis.

The UK Biobank is a general population cohort in which some of the more than 500,000 participants were diagnosed with cancer and other diseases prior to the COVID-19 pandemic. Researchers from Utrecht University and Imperial College London investigated whether a COVID-19 infection increased the risk of cancer-related mortality among partipants with cancer. They focused on cancer survivors who had been diagnosed at least five years before the pandemic, ensuring they were likely in remission. Among them, 487 individuals tested positive for COVID-19 and these were compared to 4,350 matched controls who tested negative.

After excluding those cancer patients who died from COVID-19, the researchers found that cancer patients who tested positive for COVID-19 faced an almost doubling of risk of dying from cancer compared to those patients with cancer who had tested negative. “The effect was most pronounced in the first year after infection,” said Dr. Vermeulen. The rapid progression to cancer mirrors the observed quick expansion of dormant cancer cells in the animal models.

From the second population study, the U.S. Flatiron Health database, researchers Drs. Junxiao Hu and Dexiang Gao drew data pertaining to female breast cancer patients seen at 280 U.S. cancer clinics. They compared the incidence of metastases to the lung among COVID-19-negative patients and COVID-19-positive patients (36,216 and 532 patients respectively). During the follow-up period of approximately 52 months, those patients who came down with COVID-19 were almost 50% more likely to experience metastatic progression to the lungs compared with patients with breast cancer without a diagnosis of COVID-19.

“Our findings suggest that cancer survivors may be at increased risk of metastatic relapse after common respiratory viral infections,” said Dr. Vermeulen. “It is important to note that our study focused on the period before COVID-19 vaccines were available.”

“By understanding underlying mechanisms, we will work hard to develop interventions that can limit the risk of metastatic progression in cancer survivors who experience respiratory viral infections. We also plan to extend our analyses, both in animal models and through mining of clinical data, to other cancer types and other sites of metastatic disease,” Dr. DeGregori said. “Respiratory viral infections are forever a part of our lives, so we need to understand the longer-term consequences of these infections.”             

The Nature study is titled, “Respiratory viral infections awaken metastatic breast cancer cells in lungs.” Additional Einstein authors are Lucia Petriz-Otaño, M.Sc., and Michael Papanicolaou, Ph.D. Additional CU Anschutz authors are Dexiang Gao, Ph.D., Junxiao Hu, Ph.D., Andrew Goodspeed, Ph.D., James Costello, P.hD., Shi Chia, Ph.D., Bryan Johnson, M.Sc., Felipe Valença-Pereira, Ph.D., Bennett Davenport, Ph.D., Marco De Dominici, Ph,.D., Vadym Zaberezhnyy, M.Sc., Wolfgang Schleicher and Thomas Morrison, Ph.D. Additional Utrecht University and Imperial College London authors are Marc Chadeau-Hyam and Fernando Guntoro.

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