Study finds estrogen plays hidden role in cancers, by inhibiting key immune cell

Estrogen is known to stimulate tumor growth in breast cancer cells that carry its receptors, but a new study by researchers at the Duke Cancer Institute unexpectedly reveals that estrogen plays a role in the growth of breast cancers without receptors, as well as many other cancers.

Published on September 27 in the newspaper Scientific advancesResearchers describe how estrogen not only decreases the immune system’s ability to attack tumors, but also reduces the effectiveness of immunotherapies used to treat many cancers, including triple-negative breast cancers. Triple negative breast cancers are an aggressive form of disease that is negative for estrogen, progesterone, and HER2 receptor proteins.

Informed by a retrospective analysis of patient data and experiments in mice, the researchers found that antiestrogen drugs reversed the effects of estrogen, restoring the potency of immunotherapies.

“Treatment of triple-negative breast cancer has been greatly improved with the advent of immunotherapy,” said lead author Donald McDonnell, Ph.D., professor in the Departments of Medicine, Pharmacology and Cancer Biology. , and cell biology at Duke University School. of Medicine.

“Developing ways to increase the anticancer activity of immunotherapies is a primary goal of our research,” McDonnell said. “Here we found a simple way to boost the effectiveness of immunotherapy for this type of breast cancer and the benefits have even been observed in other cancers, including melanoma and colon cancer.”

McDonnell and his colleagues, including lead author Sandeep Artham, a postdoctoral associate in the McDonnell lab, focused on a type of white blood cell called eosinophils, which are typically activated during allergic reactions and inflammatory diseases.

Eosinophils have recently been identified as being important in tumors, and a phenomenon called tumor-associated tissue eosinophilia, or TATE, is associated with better outcomes in patients with several types of cancer, including colon, breast, and esophagus, stomach, mouth, melanoma and liver.

In their studies, the Duke team described how estrogen decreases the number of eosinophils and TATE in mice. The hormone contributes to increased tumor growth in breast cancer tumors without estrogen receptors and in melanoma tumors, which do not rely on estrogen receptors for tumor growth.

Conversely, antiestrogen therapies inhibited estrogen receptor signaling and improved the effectiveness of immunotherapies, thereby slowing tumor growth.

“These findings highlight the importance of estrogen receptor signaling as a regulator of eosinophil biology and TATE and highlight the potential short-term clinical application of antiestrogen medications to increase the benefits immunotherapies in multiple tumor types,” McDonnell said.

He said clinical trials were planned with an experimental anti-estrogen drug called lasofoxifene in patients with triple-negative breast cancer.