At UT Southwestern Medical Center in Dallas, researchers have uncovered a hidden mechanism by which ovarian cancer cells evade the immune system—one that hinges on the body's own stress response. When a receptor for the stress hormone glucocorticoid switches on inside cancer cells, it orchestrates a chemical campaign that essentially mutes the immune system's ability to attack the tumor, a discovery that could reshape how doctors treat this devastating disease.
The finding matters because most ovarian tumors exist in what researchers call a "cold" state: they attract very few immune cells capable of mounting an effective defense. For years, what drives this hostile quiet has remained a mystery. Now, through work led by Dr. Suzanne Conzen, Chief of Hematology and Oncology at UT Southwestern, scientists have identified the glucocorticoid receptor as a master switch controlling that immune evasion.
The team examined ovarian cancer cells from both human and mouse sources, along with mouse tumor models and vast databases of patient data. What they discovered was striking: when the glucocorticoid receptor (GR) was activated in cancer cells, those cells released a cascade of chemical signals that summoned immune-suppressing cells into the tumor. These recruited cells—more abundant in patients who fare worse—essentially shut down the immune system's fight-back capacity. "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," Dr. Conzen said.
The researchers then tested what happens when they block this receptor. Using either a drug called relacorilant or by genetically removing the receptor from tumor cells, they found that the suppressive signals dropped dramatically. Fewer immune-suppressing cells infiltrated the tumors, while more cancer-fighting immune cells moved in. The shift was tangible—a potential window for the body's natural defenses to work.
The clinical implications are already taking shape. The Food and Drug Administration recently approved relacorilant combined with nab-paclitaxel specifically for platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer. That approval rested on earlier research from Dr. Conzen's team showing that glucocorticoid receptor activity helps cancer cells survive chemotherapy. The new findings suggest the drug may do something equally valuable: reawaken the immune system's ability to recognize and eliminate cancer cells.
Previous work from the Conzen Lab had already hinted at the receptor's importance: ovarian cancers with high glucocorticoid receptor expression were linked to shorter periods of progression-free survival in patients, meaning the disease advanced faster. These new results explain why—the receptor wasn't just helping cancer cells survive treatment; it was actively recruiting the body's own immune suppressors.
What makes this moment significant is that it opens a new therapeutic avenue. Dr. Conzen notes that future clinical trials will likely examine whether blocking the glucocorticoid receptor could enhance immunotherapy responses in ovarian cancer. For patients facing this disease, that convergence—chemotherapy, targeted immune modulation, and immunotherapy working together—could mean the difference between tumors that hide and tumors that can finally be found and defeated. The research, published in Endocrinology, represents a fundamental shift in understanding how cancer hides, and how that hiding might be undone.