Researchers at the University of Texas MD Anderson Cancer Centre have discovered that inflammation may play a key role in driving the earliest stages of lung cancer. By creating high-resolution cellular and molecular visual maps of lung cancer before and during its development, the team found that targeting proinflammatory pathways could serve as a potential early intervention strategy. The study was led by Humam Kadara, Ph.D., professor of Translational Molecular Pathology, and Linghua Wang, M.D., Ph.D., professor of Genomic Medicine. "We find that the earliest cells that give rise to lung cancer are in regions with very high inflammation and are surrounded by proinflammatory cells. By characterizing the cells and genes within precursor lesions – early-stage changes in tissues that could develop into cancer – researchers can identify potential targets for early intervention," the researchers stated. The team generated spatial transcriptomic maps of 56 human precursor lesions and advanced lung cancer samples from 25 patients. "Our work paves the way for targeting inflammation to intercept the earliest stages of lung cancer and impact patient lives." Spatial transcriptomic maps provide a visual representation of where and how genes are expressed within tissue samples. They validated their findings using an independent cohort of 36 lesions from 19 patients, providing 486,519 spots and 5.4 million cells for analysis. The researchers were able to highlight certain molecular and inflammatory changes that can distinguish precursor cells from advanced lung cancer. The study revealed that proinflammatory regions within early lesions, containing tumour-associated alveolar cells, are more active in the initial phases of cancer development and remain consistent in laboratory models, indicating that inflammation in these regions likely initiates tumour formation. "Targeting inflammation by neutralising a driver called IL-1B reduces these precursor cells of lung cancer," Kadara said.
