Wistar Study Identifies Two Genes That Protect Ovarian Cancer from the Immune System

Discovery could make immunotherapy more effective for ovarian and other cancers.

Immunotherapy has shown significant benefits in treating many cancers, especially when combined with chemotherapy. But many cancers are resistant to immunotherapy. Ovarian cancer in particular tends to respond poorly to this kind of treatment.

Now a new study by scientists at The Wistar Institute helps explain why.

The new research identifies two genes that help protect cancer cells from the immune system. While these genes are found in many types of cancer, they are especially prevalent in ovarian cancer, where they are over-expressed in as many as 25% of patients.

“Ovarian cancer has a relatively poor response to immunotherapy compared to other types of cancer,” says Rugang Zhang, Ph.D., deputy director of the Cancer Center, Christopher M. Davis Endowed Professor and program leader in the Immunology, Microenvironment & Metastasis Program, at The Wistar Institute. “So we need a new strategy.”

The discovery could lead to the development of new treatments to make ovarian cancer, and other cancers, more vulnerable to immunotherapy.

For the study, researchers scanned genes taken from mouse ovarian cancer cells, looking for genes that suppressed the immune system. They identified a complex of genes called SETDB1-TRIM28 as playing a key role in immune suppression.

They compared this to genetic data from human cancer patients and found that patients who had more expression of these genes tended to respond poorly to immunotherapy.

The findings could lead to the development of new treatments that target these genes and boost the effectiveness of immunotherapies against resistant cancers, including ovarian cancer.