The impact on a protein linked to eczema and asthma may enhance survival rates in ovarian cancer patients.

In a study published in the journal Cell, researchers found that ovarian cancer cells produce a molecule known as interleukin-4 (IL-4), which is typically associated with asthma and eczema. Cancer cells utilize IL-4 to create a protective environment that prevents access to immune killer cells, rendering tumors resistant to immunotherapy.

Ovarian cancer is one of the most lethal oncological diseases; 50% of patients die within five years of diagnosis. Unfortunately, immunotherapy drugs targeting the PD-1 molecule, which have shown effectiveness in treating melanoma and lung cancer, have not significantly improved survival rates for ovarian cancer.

This is partly explained by the fact that ovarian tumors contain fewer mutations, making it harder for the immune system to recognize them. It has now become clear that these tumors can resist immunotherapy by creating barriers that prevent immune cells from infiltrating their habitat. A crucial question, according to the researchers, was how tumors create this protective environment?

To address this question, a research team led by Alessia Baccarini, PhD, an associate professor of immunology and immunotherapy, and Brian D. Brown, PhD, director of the Icahn School of Medicine at Mount Sinai's Genomics Institute, utilized a novel genomic technology known as Perturb-map.

This technology allows researchers to determine the role of each gene in regulating the tumor environment.

Experiments revealed that the removal of the IL-4 gene from ovarian cancer cells made the tumors susceptible to PD-1 antibody therapy.

Subsequently, the researchers tested a combination of drugs that block PD-1 and IL-4 receptors in mice with aggressive metastatic ovarian cancer and found that this combined treatment significantly increased survival.

Additional preclinical studies demonstrated that ovarian cancer uses IL-4 to reprogram macrophages (a type of immune cell) into defenders of cancer cells. Macrophages reprogrammed by IL-4 prevented T-cells from destroying cancer cells.

However, by blocking IL-4, the local environment surrounding cancer cells changed, making malignant cells vulnerable to destruction by the immune system.

“Ovarian cancer is considered virtually resistant to existing immunotherapy, so we were surprised to find that by blocking just one molecule, IL-4, and altering the tumor microenvironment, we could make these hard-to-treat tumors more manageable,” says Dr. Brown. “This is further evidence that targeting not just the cancer cells, but also the tumor environment can be effective.”

Although these results are promising, the researchers emphasize that clinical trials are necessary to determine whether targeting IL-4 can improve treatment outcomes for patients.

The IL-4 pathway is already being used to treat conditions such as eczema, and researchers believe that by targeting this pathway in ovarian cancer, they can help women facing this devastating disease.