By Katarina A. Lewczyk | Date published: February 18, 2025
Siva Karthik Varanasi Investigates the Role of Bile Acids in Liver Diseases
Immunotherapy, a modern approach to cancer treatment, has proven to be much less effective for certain cancers, such as liver cancer. In a recent publication in Science, Siva Karthik Varanasi, PhD, assistant professor of medicine in the Division of Innate Immunity and a faculty member in the Program in Innate Immunity, along with his collaborators, explored the interplay between the immune system and liver microenvironment to understand why immune cells are less sensitive to immunotherapy during liver cancer and offer new molecular targets for improving liver cancer treatment and immunotherapy.
The study team found that certain bile acids in liver cancer could affect the activity of cancer-fighting immune cells, called T cells. They identified several liver bile acids associated with impaired T cell function and tumor growth. By blocking the production of these bile acids, they successfully halted tumor growth and significantly sensitized tumors to immunotherapy. Additionally, the team found that one specific bile acid, ursodeoxycholic acid (UDCA), had a positive effect on T cell activity as well as reducing existing tumors in the liver. Given that UDCA is safe in humans and is FDA approved to treat primary biliary cholangitis, Dr. Varanasi advocates that UDCA can be easily repurposed to treat liver cancer, especially in combination with immunotherapy.
“Considering how T cell performance varies across different organs, tissues, and tumors puts us at a great vantage point for looking at ways to optimize cancer treatment,” said Dr. Varanasi. “By taking this unique approach, we’re able to see that bile acids in the liver are hugely influencing T cells’ ability to do their job and, therefore, may be a useful therapeutic target.”