J&J's quest to detect lung cancer before it emerges

Smoking causes injuries in the respiratory tract that can evolve into lung cancer. Researchers from Johnson & Johnson Innovation and Boston University wondered whether it might be possible to prevent lung lesions from becoming cancerous, and now they've found biomarkers that might make such an intervention possible.

The team used mRNA sequencing to examine bronchial biopsies and brushings obtained from high-risk smokers. The researchers found genomic alterations in immune cells that might serve as indications of early development of lung cancer, according to findings published in the journal Nature Communications.

"[W]hat’s most exciting about this study is that it shows that the presence or absence of immune cells in lung pre-cancerous lesions may provide critical information as to whether that lesion will progress towards invasive lung cancer," Avrum Spira, the study’s senior author and global head of the Lung Cancer Initiative at J&J, said in a statement. "This information could one day underpin strategies to identify individuals who are incubating lung cancer and intercept the development of manifested invasive disease."

In the study, the researchers used bronchoscopy to obtain precancerous lesions repeatedly, over several years, so they could monitor whether they progressed toward or regressed away from invasive lung cancer. The biopsies were grouped into four genomic subtypes: proliferative, inflammatory, secretory and normal-like.

The researchers discovered that in the proliferative group—the most dangerous subtype that’s linked to disease progression—there was significant suppression of genes that encode for proteins involved in immune responses, including interferon signaling and antigen processing and presentation. That suggested an impaired immune environment, the team reported.

Lung cancer is the most prevalent cancer in populous countries such as the U.S. and China. The J&J-BU researchers believe their findings could help identify people facing a high risk of lung cancer and spark ideas for new preventative strategies that target the immune system.

"This research is important for the identification of patients who are early in the disease initiation process and who may benefit from interception strategies, and highlights that interventions that alter the immune system might be effective in delaying or reversing the development of lung cancer," J&J said in the statement.

Scientists often look to leverage the immune system for answers to cancer; after all, it plays a key part in identifying and destroying some cancer cells. Recent research from the Icahn School of Medicine at Mount Sinai found injection of immune stimulants directly into the tumor site, known as in situ vaccination, can instruct T cells to kill cancer cells and help patients fight off lymphoma. In another study, researchers at the University of Louisville showed a protein-based molecule could activate CD4+ T cells and natural killer cells in the immune system, and by doing that prevent healthy mice from developing cervical and lung cancers.

J&J is working with BU to create the Precancer Genome Atlas, a map of molecular and cellular changes that characterize lung lesions. They hope the information will help researchers and clinicians further improve methods for predicting and intercepting lung cancer before it emerges.They noted that the molecular alterations they found in precancerous lesions can also appear in normal airway cells. Therefore, it may be possible to identify individuals facing a high risk of lung cancer using tests that are less invasive than lung biopsies, J&J said.

by Angus Liu

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