Scientists have identified biological changes in apparently normal airway tissue that could potentially predict the development of lung cancer. The changes alter gene and cell activity in the immune system.

A team from Boston University School of Medicine in Massachusetts led the study that made these findings.

The researchers examined samples of precancerous lesions from the airway tissues of people who smoke or used to smoke. The team followed the individuals for a number of years to see whose lesions became cancerous.

In a Nature Communications paper, they describe how they identified "four molecular subtypes" of precancerous lesions with "distinct" tissue and immune system differences.

It is possible to detect the differences in airway tissue before it develops precancerous signs, says senior study author Avrum E. Spira, who is a professor of medicine, pathology, and bioinformatics at Boston University and director of its Johnson & Johnson Innovation Lung Cancer Center.

Such findings could lead to ways of screening and monitoring people who smoke and have a high risk of lung cancer, he adds, noting that they could also lead to new drugs that prevent or stop lung cancer by boosting the immune system.

Need for earlier detection of lung cancer

Lung cancer is the leading cause of cancer deaths worldwide. According to the World Health Organization (WHO), lung cancer was responsible for 1.76 million deaths in 2018.

In the US, where it accounts for around 13% of new cancers, lung cancer kills more men and women each year than cancers of the colon, breast, and prostate together, according to the American Cancer Society (ACS).

On average, a man in the US has around a 1 in 15 chance that he will develop lung cancer during his lifetime. For a woman in the US, this figure is around 1 in 17. The chance is higher for people who smoke and lower for those who do not.

One of the reasons that lung cancer kills so many people is because, while the disease usually develops slowly, it is often the case that by the time people notice the symptoms, the cancer has started to spread.

Once cancer spreads, it is more challenging to treat. Earlier detection could save many lives.

"The lung undergoes many changes prior to the development of lung cancer," says lead and corresponding study author Jennifer E. Beane, who is an assistant professor of medicine at Boston University School of Medicine.

Understanding the nature of these changes creates an opportunity to "both identify people at high risk for lung cancer and to intercept the disease process," she explains.

Helping the immune system eliminate lesions

The new research concerns the relationship between tumors and immunity. A characteristic feature of tumors is that they develop ways to evade the immune system.

"We think precancer cells might do that as well," says Prof. Spira. If that be the case, then it should be possible "to come in and find a way to train the immune system to eradicate those lesions," he adds.

He and his colleagues used "deep molecular profiling" and "bioinformatics analysis" to investigate biopsied samples of precancerous lesions from people who smoked and people who did not.

They found that samples from those who were most likely to develop lung cancer years later had much lower activity in the genes of particular types of immune cell. They named the genomic signature of the high-risk samples the "Proliferative subtype."

"Genes involved in interferon signaling and T-cell-mediated immunity," they write, "were down-regulated among progressive/persistent lesions within the Proliferative subtype compared with regressive lesions, and these pathways correlated with decreases in both innate and adaptive immune cell types."

Less invasive lung tissue sampling

The team also suggests that it should be possible to detect these changes using "brushing," which is a less invasive bronchoscope procedure for obtaining airway samples than doing biopsies.

A bronchoscope is a device that doctors and researchers use to look inside the airways of the lungs and take samples. They do this by inserting a tube containing a light and a camera into the windpipe and from there into the airways.

To obtain airway tissue samples using brushing, the investigator collects cells from the tissue surface by means of a "flexible brush" that comes out through the tube.

"Normal-appearing cells in the airway can still show you the genomic signature," says Dr. Beane.

Although it is still "early days," the findings could lead to a simpler way of testing people who might be "incubating a lung cancer and [we'd] know who to treat to intercept lung cancer," she adds.

"There is nothing [for lung cancer] like there is aspirin for colorectal cancer or statins for cardiovascular disease."

—Prof. Avrum E. Spira