The phenomenon of reactivation of disseminated cancer cells (DCC), which can remain dormant for long periods, is known, but the causal role of inflammatory processes was only suggested. For the first time, researchers demonstrate the capacity of acute respiratory infections to awaken dormant cancer cells metastasés in the lung in murine models of metastatic breast. Results that would be consistent with the increase in the number of patients developing metastases after a COVVID infection, which they also observed in two population analyzes. Their study is published in Nature.
At first, the American team exhibited mouse models, suffering from HR2+metastatic breast cancer, in the flu virus or SARS-COV-2 and observed the reactivation of dormant cells (DCC) in the lungs. It led to an expansion « massive » Cells in a few days and the appearance of metastatic lesions within two weeks. Three to 15 post-infection days, the metastatic load has been multiplied by 100 to 1,000 times, the number of Her2+ pulmonary cells remaining up to nine months. This phenomenon has not been found in mice exposed only to the antigripping vaccine.
“Dormant cancer cells are like embers and respiratory viruses are the wind that turns on the flames”explains Professor James Degregori, corresponding author of the study, professor of biochemistry and molecular genetics at the University of Colorado Denver.
An alarm clock triggered by inflammation
Respiratory infection also induces a phenotypic transition from cells: among the DCCs in mouse lungs, the percentage of HER2 cells+ expressing the Ki67 marker (phases of the mitotic cycle) increases in three days post-infection and reaches a peak to nine days. This testifies to an acceleration of cell division, typical of cancer proliferation.
Molecular analyzes have revealed an active role in interleukines-6 in the awakening of DCCs. The involvement of these cytokines, produced in abundance during a respiratory viral infection, was confirmed when the researchers used transgenic Knock-out mice for the interleukines-6: no activation of dormant cells was noted after infection by flu or SARS-COV-2. “Interleukin-6 inhibitors or other targeted immunotherapy could prevent or minimize the resurgence of metastases after viral infection”comments Professor Julio Aguirre-Ghiso, co-author of the study and professor of hematology and oncology at the Mount Sinai School of Medicine (New York).
In humans, the risk of death of double cancer after a covid infection
To find out what in humans, researchers have carried out two retrospective population studies. The first, carried out on 5,000 patients in UK Biobank Survivors of cancer diagnosed at least five years before the Pandemic of COVID-19, therefore in probable remission, highlighted an almost doubled risk of cancer deaths in those who had already been tested positive at SARS-COV-2 (ODDS RATIO OR = 1.85). The effect was particularly pronounced in the first post-infection year, which joined the observations on the mice of a rapid metastatic expansion.
The second study draws its data from the U.S. Flatiron Health database which lists 36,800 women affected by a first breast cancer. Again, patients who had a COVVI-19 infection had a greater probability of developing pulmonary metastases (Hazard Ratio HR = 1.44).
“By understanding the underlying mechanisms, we will be able to work to develop interventions limiting the risk of metastatic progression in cancer survivors who had a respiratory infection”indicates Professor Degregori. And add: “Respiratory infections will always be part of our lives, so we must understand the long -term consequences. »»
A plea for vaccination
In a reaction on the Science Media CentreProfessor Andreas Berthalger, director of the Institute of Hygiene and Immunology Applied at the University of Medicine in Vienna, qualifies the results “Innovatives and potential great clinical relevance”. He adds: “The study provides mechanistic evidence of the way in which respiratory viral infections reactivate disseminated dormant cells and promote metastasis. »»
He salutes the relevance of these murine models which “Seem particularly suitable for the questions asked since the dormancy phase of cancer cells is long, up to a year, which reflects the situation in humans”. Moreover, “The signaling pathways of IL-6 are highly preserved between mice and humans”.
“The contribution of an inflammatory response caused by a chronic infection (hepatitis C for example) to the development of cancer is already known. The novelty and interest here are that acute respiratory infections can lead to the development of metastases mediated by the inflammatory response ”comments Professor Carsten Watzl, director of the Leibniz Research Center for Working Environment and Human Factors Research Research Unit of Dortmund. The expert calls for “Consider these respiratory infections seriously. Individuals should be vaccinated to protect themselves from the disease and hopefully, from its secondary consequences. »»
