Researchers found that PGE2, which is produced normally by epithelial cells but at very high levels in lung cancer and other malignancies, up-regulates the activity of lymphocytes called T-regulatory cells, which suppress immune function, making it even harder for a patient to fight cancer. For the first time, UCLA researchers showed that PGE2 increases the growth and function of T-regulatory cells, making them more effective immune suppressors, said Dr. Steven Dubinett, director of the Lung Cancer Research Program at UCLA's Jonsson Cancer Center and senior author of the study.
The study appears in the July 15, 2005, issue of the peer-reviewed Journal of Immunology.
"We know that COX-2 inhibitors like Celebrex decrease PGE2, so when we discovered that PGE2 was fueling the T-regulatory cells, we knew we had a therapy we could test," said Dubinett, also a professor of pulmonary and critical care medicine and director of the Specialized Program of Research Excellence (SPORE) in lung cancer. "This discovery opens up the possibility that we could utilize relatively non-toxic drugs to augment immune responses in cancer patients."
The COX-2 inhibitors could be given with chemotherapy and immunotherapy drugs to help boost immune function in patients and help them to better fight cancer, Dubinett said.
Dubinett and his research team had hypothesized that PGE2 might be involved in suppression of the immune system. They first tested the theory in animal models and found that PGE2 was fueling the growth and function of the T-regulatory cells. Using Celebrex, researchers were able to decrease in number and function the T-regulatory cells by blocking PGE2. That study appeared in
Contact: Kim Irwin
University of California - Los Angeles