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Studying how mice respond to infection by respiratory viruses may hold the answers to inhibiting the spread of metastatic breast cancer, according to a new study.

Metastatic cancer is when the disease has spread from the area it started to other areas of the body. The lungs are one of the most common sites of metastasis.

New collaborative research from ÌìÃÀ´«Ã½ and the Francis Crick Institute shows that when the immune system is triggered by a respiratory virus it can temporarily make the lungs a more hostile environment for incoming cancer cells.

In an experimental study in mice, they found that this immune response reduced the number of metastatic breast cancer tumours that formed in the lungs.

Highlighting the approach in their paper, published in the journal PNAS (Proceedings of the National Academy of Sciences), the researchers focused on Respiratory Syncytial Virus (RSV), a common virus.

Fewer tumours

When lung cells detect such viruses, they release type I interferons - molecules that help to stop viral replication. But the researchers found that the same type I interferons also disrupted the earliest steps of cancer cell metastasis. In experiments mimicking the spread of cancer, breast cancer cells were introduced into mice that had recently experienced RSV infection. They developed fewer lung tumours than a control group of uninfected mice.

It wasn’t the growth, it was the entry of the cancer cells into the lungs that had changed.” Dr Ana Farias National Heart and Lung Institute

First author Dr Ana Farias, of ÌìÃÀ´«Ã½’s National Heart and Lung Institute, says: “We found that 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 of the cancer cells into the lungs that had changed.”

Dr Ilaria Malanchi at the Crick Institute said: “Our study emphasises the importance of the host environment in either helping or hindering cancer from spreading to a new part of the body - in this case the environment in the lung post-infection helps to stop cancer from infiltrating the lung. 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.’ 

The study shows that type I interferons reshape the lung environment, making it harder for cancer cells to “seed” and establish new tumours. The team also identified Galectin‑9  - a protein produced in response to interferons  -  as a key player that can directly interact with cancer cells and reduce their ability to spread.

Identifying new drug targets

This work suggests that the immune landscape created by a viral infection may offer a short-lived protective window against metastatic spread to the lungs. If the findings in mice can be replicated in humans, it could have implications for treatment of metastatic cancer. While the researchers emphasise that a respiratory virus won’t in itself be a future treatment, by understanding the mechanisms behind this effect, they hope that new and effective drug targets might be found that could one day help slow or prevent cancers metastasising.

Professor Cecilia Johansson said: “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 effect we have observed.”

Tanya Hollands, Research Information Manager at Cancer Research UK, which part-funded the research, said: "Thanks to research, breast cancer survival in the UK has doubled over the past 50 years, but too many women still die from advanced disease. It’s not fully understood how and why some types of breast cancer spread to other parts of the body.

“This study suggests that certain viral infections influence how the immune system interacts with cancer cells. RSV in particular appeared to prime the immune system to limit the spread of breast cancer cells to the lungs in mice.

“This is early-stage research, and previous studies have reported different effects, so more work is needed to understand what this could mean for people. But uncovering how the immune system shapes cancer’s ability to grow and spread could potentially help us find new ways to beat it.”

The collaborative research was funded by grants to Cecilia Johansson and Ilaria Malanchi from Cancer Research UK and the Medical Research Council.