Kathryn A. O'Donnell, PhD

The chemical lactate serves as a fuel in normal tissue and in cancer. Our research suggests that targeting how cancer cells make or transport lactate could be a useful way to treat lung cancer. We used a screening method on human lung epithelial cells to find new genes that help drive lung cancer. One of the genes we found is TMPRSS11B, which makes a protein found on the surface of cells. This gene is more active in lung squamous cell carcinoma (LUSC) than in normal lung epithelial cells and higher levels of it are linked to worse survival in lung cancer patients. When we increased TMPRSS11B in LUSC cells, their ability to form tumors grew. When we reduced it, tumor growth slowed down. TMPRSS11B also helped the cells get rid of lactate more effectively, which supported tumor growth. We will continue to investigate the role of lactate metabolism in LUSC.

Courtney Cox Cole Lung Cancer Research Award

Update: Our laboratory studied how a protein called TMPRSS11B helps lung squamous cell carcinoma (LUSC), a type of lung cancer, grow and progress. We previously found that TMPRSS11B helps cancer cells produce energy and remove lactate, an important metabolite that can acidify the tumor microenvironment and suppress immune cells. In this study, we examined how TMPRSS11B affects the immune system and the environment around a tumor. We found that reducing TMPRSS11B greatly decreased tumor growth in mice with normal immune systems and allowed more immune cells to enter the tumors. Using advanced imaging, genetic and metabolic analysis, we found that TMPRSS11B was especially active in a specific group of cancer cells within LUSC tumors. We also found that areas with high TMPRSS11B activity had more acidity, higher levels of lactate and more immune cells called macrophages that can suppress the body's ability to fight cancer. These findings show that TMPRSS11B helps create a tumor environment that supports cancer growth and weakens the immune response. The study identifies TMPRSS11B as a potential target for new LUSC treatments.