HMN 2026: How Ovarian cancer cells use stress hormone signaling to shut down immune system

When activated in ovarian cancer cells, the receptor for the body’s primary stress hormone alters the tumor environment in ways that blunt immune response, according to new research led by UT Southwestern Medical Center. The findings, published in Endocrinology, identify a previously unrecognized role for the glucocorticoid receptor (GR) in shaping the ovarian cancer tumor microenvironment.

“Understanding master regulators (like GR) of tumor cell evasion from the immune system could lead to more effective treatment of ovarian cancer—both in combination with chemotherapy and eventually with immunotherapy,” said corresponding author Suzanne Conzen, M.D., Professor of Internal Medicine, Chief of the Division of Hematology and Oncology, and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Most ovarian tumors exist in a so-called “cold” state, meaning they attract few immune cells needed to mount an effective attack, but what drives that state has been poorly defined.

The Conzen Lab previously found that ovarian cancers with high GR expression are linked to shorter periods of progression-free survival among patients, suggesting the receptor plays an important role in how the disease progresses.

In the new study, the team examined ovarian cancer cells from humans and mice, mouse tumor models, and large databases of patient tumor data.

They found that when GR was switched on inside cancer cells, the cells released a mix of chemical signals that summoned immune-suppressing cells into the tumor. Those recruited cells, which are more abundant in patients with worse outcomes, shut down the immune system’s ability to attack the cancer.

When the researchers blocked GR, either with a drug called relacorilant or by genetically removing the receptor from tumor cells, the suppressive signals dropped. Fewer immune-suppressing cells made their way into tumors, and more of the immune cells that fight cancer moved in.

The findings also align with clinical progress already underway. The Food and Drug Administration recently approved relacorilant combined with nab-paclitaxel for platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer.

The Phase III trial supporting that approval was based on a series of earlier research from Dr. Conzen and her colleagues showing that GR activity helps ovarian cancer cells survive chemotherapy. The new UTSW findings suggest the drug may also reawaken antitumor immunity.

“Future clinical trials will likely examine whether GR modulation could assist with immunotherapy responses in ovarian cancer,” Dr. Conzen said.

The content is provided for information purposes only.