Uncovering Sex-Specific Immune Differences in Glioblastoma

By: Rachel Tompa, Ph.D. | June 23, 2026 | 7 min. read |

Dr. Defne Bayk, outside on the Miller School medical campus

Summary

A new preclinical study uncovers sex differences in how the immune system may respond to the brain cancer glioblastoma.
In females, the cancer is driven by interactions between the neurotransmitter GABA and a specific type of immune cell.
There may be new drug targets in this interaction that could lead to therapeutics specifically for women with glioblastoma.

Men and women experience many diseases very differently. Certain diseases present more commonly in one sex than in another. Some conditions like heart attacks may cause different symptoms in men and women. Some treatments work better or not at all for one sex over the other.

Cancer is no exception. There are major differences in male and female immune systems, a system critical for cancer’s growth and for successfully becoming cancer-free. For example, some immunotherapies work better in men than in women and vice versa.

Glioblastoma, the most common and fatal form of brain cancer, is more common and more deadly in men than in women. The reasons behind this difference and how the cancer’s biology differs between men and women remain largely unclear.

Now, a study led by researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine , has identified a cellular mechanism that differs between male and female laboratory models with glioblastoma. The study was published in the journal Nature Cancer and led by Defne Bayik, Ph.D., assistant professor of molecular and cellular pharmacology at the Miller School, and Asmita Pathak, Ph.D., a former postdoctoral fellow in the Bayik Lab.

“We have a growing appreciation that cancer doesn’t act the same way in men and women. There are differences in incidence rates. There are differences in treatment responses. There are differences in outcomes,” Dr. Bayik said. “But we don’t really have a good, fundamental understanding of the mechanisms underlying these observational studies.”

Delving Into Immune Differences

To uncover that mechanism for glioblastoma, Dr. Bayik and her colleagues focused on a certain class of immune cells in the brain known as myeloid-derived suppressor cells, or MDSCs. As their name suggests, these cells suppress other cells’ immune activity, especially that of T cells. In healthy contexts, their activity is important for regulating the immune system and keeping inflammation under control. But in the context of cancer, these cells are often recruited by tumors to suppress surrounding T cells and other immune cells, protecting cancerous cells from the rest of the immune system and allowing them to grow unchecked.

In previous work, Dr. Bayik found sex-specific differences in the immune landscape of glioblastoma, with higher levels of monocytic myeloid-derived suppressor cells associated with disease in male laboratory models. Granulocytic MDSCs play a more prominent role in females. In studies of human glioblastoma tumors, she observed a similar pattern. Men tend to have more monocytic MDSCs within their tumors, Granulocytic MDSCs, or proteins associated with these cells, correlate with worse outcomes for women but not for men.

Women still constitute 40% of glioblastoma patients. By identifying these differences, we can better tailor treatments for both men and women.
Dr. Defne Bayik

In the new study, Dr. Bayik and her colleagues wanted to understand what drives this difference. How do granulocytic MDSCs act to promote cancer growth in female but not male laboratory models? In Dr. Bayik’s previous study, she’d found several drug candidates that are predicted to act on granulocytic MDSCs. A few of these candidate drugs target proteins related to GABA, a brain signaling molecule also known as a neurotransmitter.

By exposing different populations of MDSCs to GABA in the lab, the scientists found that the neurotransmitter specifically affects cellular metabolism only in female granulocytic MDSCs. The process is unaffected in male MDSCs. They also found that this reprogramming of the cells’ metabolism by GABA made the granulocytic MDSCs more immunosuppressive. Finally, they found that blocking the GABA receptor in female laboratory models with glioblastoma improved their outcome. This had no effect on male laboratory models with the cancer.

Potential for Treatment Personalized by Sex

Dr. Bayik and her colleagues found that many of their lab findings held up in human samples donated by patients with glioblastoma. Tumor biopsies from women had higher levels of GABA and the GABA receptor in granulocytic MDSCs than did those from men. They also found that GABA reprograms granulocytic MDSC metabolism in women as it does in lab models.

These findings point to the potential for a sex-specific treatment for glioblastoma, Dr. Bayik said. She’s currently working to understand the basis for the difference in cellular metabolism in these immune cells between male and female laboratory models. Further uncovering the mechanism of this sex difference will help her and other scientists find new potential drug targets for the disease. MDSCs are involved in many other types of cance. Drugs that target these cells could have broader applications than just glioblastoma.

“Glioblastoma may be more common in men, but women still constitute 40% of patients,” said Dr. Bayik. “By identifying these differences, we can better tailor treatments for both men and women.”