A Breath of Bad Air
How exposure to air pollution causes dormant cells to form tumors
George Francis Lee | | News
Since the industrial revolution, increasing levels of emissions in our immediate and global atmosphere have, unsurprisingly, had a detrimental impact on our health. But what is surprising is how exposure to these emissions drives the formation of lung cancer. According to the authors of a new study, it is the inflammation caused by air pollution that causes naturally dormant mutations to “wake,” activate, and develop into tumors (1).
“These rare cells are normally dormant,” says co-author Clare Weeden, researcher at the Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. “But inflammation triggered by air pollution inhalation wakes them up and increases their likelihood of forming tumors.” Interestingly, in the team’s experimental model, they found that if inflammation was blocked during exposure to air pollution, tumor development was avoided.
The paper focused on cases of EGFR-driven lung cancer – particularly people who have never smoked. “About 10–25 percent of lung cancer cases worldwide occur in people who never smoke,” says Weeden, “We have changed how we view lung cancer in people who never smoke and identified one way in which cancer can be triggered in this group – through air pollution exposure.”
The team found that air pollution interacts with what they call a “tumor promotion” mechanism – something that was first hypothesized in research of tumorigenesis over 70 years ago. Using mouse models, the team found that air pollutants lead to a deluge of macrophages within the lungs, which then release cytokine interleukin-1β. It’s this process that “promotes” the generation of tumors, particularly within EGFR mutant lung alveolar type II epithelial cells. The researchers also revealed that EGFR and KRAS driver mutations were found in 18 and 53 percent of lung tissue samples from a study cohort, respectively.
The researchers hope their findings may lead to new options for cancer prevention – even point us towards a way to reverse tumorigenesis. “The mechanism we identified could lead us to find better ways to prevent and treat lung cancer in never-smokers,” says Weedan. “Our next steps are to find who might be most at risk of this cancer and see if there are any novel therapies that might stop cells from growing in response to pollution.”
- W Hill et al., “Lung adenocarcinoma promotion by air pollutants,” Nat, 616, 159 (2023). PMID: 37020004.