Key Findings and Potential Implications

Researchers at UT Southwestern Medical Center have discovered how a hormone interacts wiht a receptor on the surface of immune cells to shield cancer cells from the body’s natural defenses. The findings, published in Nature Immunology, could lead to new immunotherapy approaches for treating cancer as well as potential treatments for inflammatory disorders and neurologic diseases.

The research centers on myeloid cells, a type of immune cell often found at tumor sites. These cells initially attempt to fight cancer but quickly transition to supporting tumor growth. The study suggests a hormone stimulates receptors on these myeloid cells, suppressing the immune system and allowing cancer to evade detection.

“myeloid cells are among the first group of immune cells recruited to tumors, but very quickly these tumor-fighting cells turn into tumor-supporting cells. Our study suggests that receptors on these myeloid cells get stimulated by this hormone and end up suppressing the immune system,” said Cheng Cheng “Alec” Zhang, Ph.D., Professor of Physiology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Zhang co-led the study with first author Xing Yang, Ph.D., a postdoctoral researcher in the zhang Lab.

Current immunotherapies, such as immune checkpoint inhibitors, are effective for only about 20%-30% of cancer patients, Dr. Zhang noted, indicating that cancers employ multiple strategies to avoid immune attack. This research identifies a previously unknown mechanism of immune evasion.

Researchers in the Zhang Lab previously identified an inhibitory receptor called LILRB4. Stimulating this receptor blocked the myeloid cell’s ability to suppress the immune system. Further investigation revealed the hormone responsible for activating LILRB4 and triggering the immunosuppressive effect.

The Role of LILRB4 and the identified Hormone

The inhibitory receptor LILRB4 plays a crucial role in the process. When activated by the hormone, it effectively puts the brakes on the immune response, allowing cancer cells to proliferate. The specific hormone involved has not been publicly disclosed in the initial reporting, but further research is expected to reveal its identity.

Understanding this hormone-receptor interaction opens avenues for developing therapies that block the interaction, thereby restoring the immune system’s ability to target and destroy cancer cells. This approach could potentially enhance the effectiveness of existing immunotherapies or provide new treatment options for patients who don’t respond to current methods.

Potential applications Beyond Cancer

The implications of this finding extend beyond cancer treatment. Becuase the immune system plays a role in both inflammatory and neurological disorders, modulating this hormone-receptor pathway could offer therapeutic benefits in these areas as well.

For example, in autoimmune diseases, where the immune system mistakenly attacks healthy tissues, blocking the hormone’s action could help to dampen the immune response and reduce inflammation. Similarly, in neurological diseases involving neuroinflammation, modulating this pathway could potentially protect nerve cells from damage.

Study Details and Methodology

The study, published in Nature Immunology on September 22, 2025, involved a combination of in vitro (laboratory) and in vivo (animal) experiments. researchers used cell cultures and animal models to investigate the interaction between the hormone, LILRB4, and myeloid cells. They demonstrated that blocking the hormone-receptor interaction could restore immune function and inhibit tumor growth in the animal models.