The immune response to respiratory viruses in mice may hold the answers to inhibiting the spread of breast cancer.
Breast cancer metasases in mouse lungs. Credit: Ana Farias, PNAS.
Tumours can’t grow without corrupting healthy cells and creating a ‘pro-cancer’ environment in which they can thrive. For cancer biologist Ilaria Malanchi, who leads the Crick’s Tumour-Host Interaction Laboratory, understanding how cancer interacts with healthy cells in the body is key to how we might treat it.
“Cancer can spread beyond its original site, in a process called metastasis,” Ilaria says. “This is a big problem for breast cancer, which becomes much harder to treat if it spreads. We’re interested in how cancer cells signal to new tissues, such as in the lungs, to make the environment more supportive for the growth of a tumour.”
The flow of air into our lungs as we breathe exposes them to microbes, allergens and pollution constantly, so immune cells here are carefully restrained to avoid damaging these critical organs. Researchers believe that tumours might take advantage of this tightly controlled immune system, which could explain why the lungs are the second most frequent site for metastasis.
To delve deeper, Ilaria’s team joined forces with Cecilia Johansson at Imperial College London’s National Heart and Lung Institute to explore how cancer spread to the lung might be affected during the fight against a viral infection.
In a study published this week in the journal PNAS, the researchers explored the impact of respiratory syncytial virus (RSV), the common cause of coughs and colds, on the lung environment. When lung cells detect viruses like RSV, they release type 1 interferons, immune molecules that help to stop viral replication.
“To mimic the spread of cancer into the lungs, we introduced breast cancer cells into mice that had recently experienced RSV infection,” says Ilaria. “Fascinatingly, they developed fewer lung tumours than mice that hadn’t previously experienced RSV infection.”
First author Ana Farias, also at Imperial, added, “Mice that had recently experienced a respiratory virus infection had fewer, although not smaller, tumours. So it wasn’t the growth, it was the entry into the lungs that had changed.”
Fewer metastases (darker areas) were seen in the lungs of mice with RSV infection (right) than in the lungs of mice without RSV infection (left), although the size of the tumours was similar. Credit: Ana Farias, PNAS.
The team showed that, in mice, it was the immune mediator, type I interferons, that could reduce viral spread but also disrupt the earliest steps of cancer cell metastasis. This was because they reshape the lung environment, making it harder for cancer cells to ‘seed’ and establish new tumours.
“Type I interferons were able to disrupt the interactions between cells lining the airways in the lung, called epithelial and endothelial cells, and cancer cells,” explains Ilaria. “RSV infection also increased the amount of a protein called Galectin-9, responsible for both enhancing the immune response to the virus, but also stopping cancer cells from taking hold.”
Mice were intranasally exposed to interferon-a or RSV virus (shown in image). Both induced the production of Galectin-9 (green areas in the right-hand panel). Credit: Ana Farias, PNAS.
Interestingly, RSV infection itself wasn’t necessary to create an anti-cancer environment. The team found that administering type I interferons to mice that hadn’t experienced RSV infection or exposing the tumour cells to Galectin-9 was sufficient to restrict metastatic seeding. This suggests that it’s the environment created by a viral infection, rather than the virus itself, that is important in creating a short-lived protective window against cancer.
The researchers are keen to emphasise that a respiratory viral infection itself won’t be a future treatment, but by understanding the mechanisms behind this effect, they hope that new and effective drug targets could be found that might one day help slow or prevent cancers spreading.
Cecilia says, “If we can find a way of making lungs more ‘resistant’ to successful seeding of metastatic cancer cells, that’s encouraging. Going forward, we hope a drug could be developed to mimic the effects we have observed.”
For Ilaria, the study emphasises the importance of the host environment in either helping or hindering cancer from spreading to a new part of the body. “Studies in humans will now be important to confirm whether this effect is seen in people, and how we could exploit this knowledge to find new ways to stop cancer spread,” she concludes.
Adapted from an article from Imperial College London.
