Researchers at UT Southwestern Medical Center have discovered how a hormone interacts with 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.

“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 said, suggesting that there are multiple ways that cancers evade attack from the immune system.

Several years ago, researchers in the Zhang Lab studying cancer-fighting immune cells called myeloid cells identified an inhibitory receptor called LILRB4. Stimulating this receptor blocked the myeloid cells’ ability to attack tumors.

Dr. Zhang, Dr. Yang and their colleagues then did a genome-wide screen of all proteins that might interact with LILRB4.

A promising hit was a hormone called SCG2. Although researchers have suggested that SCG2 plays a role in immune response, its function and receptor were unknown.

Laboratory experiments confirmed that SCG2 binds to LILRB4, kicking off a signaling cascade that turned off the cancer-fighting abilities of myeloid cells and inhibited their ability to recruit cancer-fighting T cells to tumors.

In mice genetically altered to express the human form of LILRB4, injected cancer cells that produced SCG2 grew rapidly as tumors. Treating these mice with an antibody that blocks LILRB4 significantly slowed cancer growth, as did artificially ridding the animals’ bodies of SCG2.

Together, these experiments suggest that interactions between LILRB4 and SCG2 allow cancer to grow unchecked by myeloid cells, T cells, and potentially other immune cell types.

Dr. Zhang suggested that disrupting this interaction could someday offer a new immunotherapy option to treat cancer.

Conversely, because this interaction neutralizes myeloid cells’ immune activity, delivering extra SCG2 could be a promising treatment for autoimmune or inflammatory disorders spurred by myeloid cells. Dr. Zhang and his colleagues plan to investigate both ideas in future studies.