Scientists at the Salk Institute — including Director of the NOMIS Center for Immunobiology and Microbial Pathogenesis Susan Kaech, NOMIS researcher Gerald Shadel, former NOMIS Fellow Siva Karthik Varanasi and NOMIS Fellow Dan Chen — have discovered that removing the bile acid–creating protein BAAT and adding the bile acid UDCA controls tumor growth in mice with liver cancer. Their findings were published in Science.
Immunotherapy is a modern approach to cancer treatment that uses a patient’s own immune system to help fight tumors. It has made an incredible impact on treating cancers in many different organ systems, including the lung, kidney, and bladder—but for other cancers, such as liver cancer, the therapy has been much less effective. This discrepancy is especially concerning as liver cancer rates have nearly tripled in the last 40 years.
To understand why immunotherapy may be less effective in treating liver cancer, scientists at the Salk Institute took a closer look at how the immune system and liver interact. While studying mouse and human liver tumors, they discovered that certain bile acids in the liver could affect the activity of cancer-fighting immune cells, called T cells.
The researchers identified several liver bile acids associated with impaired T cell function and tumor growth, and were able to successfully halt tumor growth and shrink existing tumors by blocking their production. They also saw that one specific bile acid—ursodeoxycholic acid (UDCA) —had a positive effect on T cell activity in the liver. In fact, boosting the levels of this bile acid through dietary supplementation was enough to control tumor growth in mice with liver cancer. Because these supplements are already commercially available and used to help treat other liver diseases, the researchers are hopeful that UDCA could be incorporated into liver cancer treatment plans to make immunotherapy more effective for these patients.
The findings, published in Science on January 9, 2025, help explain why immune cells behave differently in different tumor environments and offer several new molecular targets for improving liver cancer treatment and immunotherapy.
“How do organ-specific properties and processes influence the immune response?” asks Professor Susan Kaech, senior author of the study and director of Salk’s NOMIS Center for Immunobiology and Microbial Pathogenesis. “Livers have a particularly unique environment, but we didn’t really understand how it was affecting the immune and cancer cells. By investigating these liver-specific features, we have identified several potential ways to regulate bile acids, improve T cell performance, and enhance patient outcomes.”
Continue reading this Salk release: Bile acids exacerbate liver cancer, dietary supplement may offer relief
Read the Science publication: Bile acid synthesis impedes tumor-specific T cell responses during liver cancer
Feature image: Low magnification micrograph of hepatocellular carcinoma, the most common form of primary liver cancer, i.e., the most common form of cancer to arise in the liver. (Photo: Nephron, CC BY-SA 3.0, via Wikimedia Commons)
