Viral Infections May Protect Against Cancer Spread
Respiratory infections trigger interferons that make the lungs less hospitable to metastatic cancer cells.
The immune response to viral infections in the lungs may prevent a “pro-cancer” environment from forming.
New research has identified type 1 interferons induced by viral infection as a key player in impairing the initiation of breast cancer spread to the lungs.
Metastasis—the spread of tumor cells from the primary site to other sites in the body—is a significant cause of cancer mortality. In breast cancer, metastasis accounts for 90% of deaths, with the lungs being a common site of cancer spread.
The lung microenvironment benefits cancer spread
The lungs are constantly exposed to airborne pathogens, allergens, and pollutants. The immune cells in the lungs are therefore carefully constrained to prevent overactivation of the inflammatory response that could cause damage.
This high threshold for immune cell activation could benefit cancer cells during metastasis, as they may go undetected or avoid activating the immune system as they spread into the lung tissue.
Respiratory virus infections distinctly alter the lungs. In respiratory virus infections, a pro-inflammatory response rapidly activates resident immune cells and recruits innate immune cells to limit viral replication, clear viruses, and protect against future infection.
These immune changes to the lung microenvironment may influence how cancer cells metastasize.
Type 1 interferon alters the lung environment during infection
To explore how cancer spread to the lungs might be affected by the response to viral infection, researchers introduced breast cancer cells into mice that had recently been infected with respiratory syncytial virus (RSV)—a common cause of coughs and colds.
“Mice that had recently experienced a respiratory virus infection had fewer, although not smaller, tumors. So, it wasn’t the growth, it was the entry into the lungs that had changed,” explained Dr. Ana Farias, a research associate at Imperial College London and first author of the new research.
During RSV infection, type 1 interferons—important antiviral cytokines that regulate lung inflammation—are produced by alveolar macrophages. They inhibit viral replication and recruit and activate immune cells. Type 1 interferons are also known to have both anti- and pro-tumor roles in cancer immunity.
The researchers used single-cell RNA sequencing to study how type 1 interferons influence the interactions between lung cells and metastatic cancer cells.
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“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,” said Dr. Ilaria Malanchi, who contributed to the work.
Type 1 interferon-mediated changes in the lung environment created a less supportive niche for cancer cells to colonize and grow. This made it more difficult for cancer cells to “seed” and establish new tumors in the lungs.
“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,” Malanchi noted.
The researchers also administered IFN-α, a major type 1 interferon, to mice independently of viral infection, and observed a transient inflammatory response. They then administered IFN-α prior to introducing cancer cells to the mice.
“Remarkably, compared to the control group, IFN-α exposure resulted in a reduced number of metastatic nodules in the lung, to a similar extent as RSV infection,” the authors reported in the paper.
Exposing cancer cells to Galectin-9 also reduced their ability to colonize the lungs.
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This indicates that the environment created by RSV infection, rather than the virus itself, restricts metastasis.
A therapeutic avenue to slow metastasis
Determining the key changes induced in epithelial cells by type 1 interferons and the mechanisms behind their effects could point to new drug targets for the development of therapeutics that could slow or prevent cancer metastasis.
“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,” said Professor Cecilia Johansson, who also contributed to the research.
“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,” concluded Malanchi.
Reference: Farias A, Bridgeman VL, Rodrigues FS, et al. Type I interferons induced upon respiratory viral infection impair lung metastatic initiation. PNAS. 2026;123(16):e2412919123. doi: 10.1073/pnas.2412919123
This article is a rework of a press release issued by The Francis Crick Institute. Material has been edited for length and content.
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