Inflammation identified as a key driver in the earliest stages of lung cancer

By creating high-resolution cellular and molecular visual maps of lung cancer before and during development, researchers at The University of Texas MD Anderson Cancer Center have discovered that the earliest stages of lung cancer may be driven by inflammation, suggesting that targeting proinflammatory pathways could be an early intervention approach.

The study, published today in Cancer Cell, generated spatial transcriptomic maps in precancerous and more advanced stages of lung cancer to provide a deeper understanding of early lung cancer development. The research was led by Humam Kadara, Ph.D., professor of Translational Molecular Pathology, and Linghua Wang, M.D., Ph.D., professor of Genomic Medicine, associate member of the James P. Allison Institute™ and focus area co-lead with the Institute for Data Science in Oncology.

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. Targeting inflammation by neutralizing a driver called IL-1B reduces these precursor cells of lung cancer. Our work paves the way for targeting inflammation to intercept the earliest stages of lung cancer and impact patient lives."

Humam Kadara, Ph.D., Professor of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center

What is spatial transcriptomics and how does it help identify targets for cancer progression?

Spatial transcriptomic maps provide a visual representation of where and how genes are expressed within samples. Characterizing the cells and genes in precursor lesions – early-stage growths or changes in tissues that have the potential to develop into cancer – can identify potential targets for early intervention.

The researchers generated spatial transcriptomic maps of 56 human precursor lesions and advanced lung cancer samples from 25 patients. 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.

How do these findings help patients with lung cancer?

The researchers were able to highlight certain molecular and inflammatory changes and characteristics that can distinguish between precursor cells and advanced lung cancer.

For instance, there are proinflammatory areas within precursor lesions that have alveolar cells associated with tumors. These proinflammatory regions also are more active and more prevalent in earlier phases of lung cancer development, and are conserved in lab models of lung cancer, suggesting that inflammation in these regions is likely initiating tumors.

The findings show that targeting inflammation alone or in combination with immunotherapy may be promising early interception strategies for lung cancer.