Immunotherapy is a treatment that helps the body’s own immune system fight cancer. It has worked well for several cancers like those of the lung, kidney, and bladder.
But when it comes to liver cancer, the results have not been very successful. This is a major concern because liver cancer cases have increased almost three times in the last 40 years.
To find out why liver cancer does not respond well to immunotherapy, researchers at the Salk Institute studied how the immune system interacts with the liver. They looked at both mouse models and real tumor samples from people.
What they found was surprising—certain bile acids made by the liver to help digest fats can weaken the immune system’s T cells, which are needed to kill cancer cells.
The researchers identified specific bile acids that made T cells less effective, allowing tumors to grow faster. But they also found one bile acid that had the opposite effect. It’s called ursodeoxycholic acid, or UDCA. This bile acid actually helped T cells work better in the liver.
When the team gave mice UDCA supplements, their liver tumors shrank. Because UDCA is already used as a treatment for other liver problems, it could be quickly tested to see if it helps make immunotherapy work better for liver cancer patients.
This study, published in the journal Science, helps explain why immune cells don’t work the same in every part of the body. It also opens new doors for improving liver cancer treatment by targeting specific bile acids.
Professor Susan Kaech, senior author of the study, said the liver is a unique organ, and researchers didn’t fully understand how it affects immune cells and cancer cells. By focusing on liver-specific factors like bile acids, the team discovered new ways to help T cells function better and possibly improve outcomes for people with liver cancer.
The liver makes over 100 types of bile acids. These acids help with digestion but also create a tough environment for immune cells. In earlier research, high levels of bile acids were linked to worse health and more cancer, but scientists hadn’t studied how each specific bile acid acts.
Former Salk researcher Siva Karthik Varanasi explained that understanding how T cells work differently in each organ is crucial to improving cancer care. Their study shows that bile acids in the liver strongly affect how well T cells can do their job.
The team studied liver cancer tissue from humans to see which bile acids were present. They noticed that some harmful bile acids, called conjugated bile acids, were found in higher amounts.
These acids are made with the help of a protein called BAAT. When researchers blocked this protein in mice, the tumors shrank. This means that targeting BAAT in people might also improve cancer treatment.
The scientists went on to test 20 different bile acids to see how each one affected T cells. One bile acid, called TCDCA, caused damage by creating oxidative stress.
Another, called LCA, harmed the T cells by stressing parts of the cell responsible for making proteins. But UDCA stood out because it actually improved T cell function and brought more immune cells to fight the tumor.
When they gave mice UDCA supplements, their liver tumors became smaller. This result shows that increasing UDCA and lowering BAAT could be a new way to help the immune system fight liver cancer more effectively.
Kaech said they are hopeful because UDCA is already approved for other liver diseases, making it easier to start clinical tests in liver cancer patients.
She also said they are now looking at how the gut microbiome—the bacteria living in our intestines—could play a role in controlling bile acids. This raises new questions: Can we use “good” bacteria or probiotics to help fight liver cancer? How does the microbiome change during liver cancer?
The team believes that other health problems like chronic liver disease and obesity, might also benefit from lowering harmful bile acids, especially those made with BAAT.
If you care about liver health, please read studies that refined fiber is link to liver cancer, and the best and worst foods for liver health.
For more health information, please see recent studies about how to boost your liver naturally, and simple ways to detox your liver.
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