A RECENT study sheds light on how estrogen signaling affects immune response in breast cancer, potentially opening pathways for combined anti-estrogen and immunotherapy approaches. The research from the University of Illinois reveals that estrogen may hinder the body’s immune defense by reducing the activity of eosinophils. This immune suppression could contribute to the more favorable conditions for tumor progression observed in estrogen-sensitive breast cancers.
Estrogen’s impact on eosinophils, specifically in the context of breast cancer, emerged as a focal point of the study. Eosinophils, typically associated with asthma and allergic responses, are also active in immune responses within tumor tissue, where they are known as tumor-associated tissue eosinophils (TATE). These cells have shown promise in enhancing the effectiveness of immune checkpoint blockade (ICB) therapies, which rely on the immune system to target and destroy cancer cells. However, the researchers discovered that estrogen signaling suppresses eosinophil activity, both in general circulation and within tumors, leading to reduced immune response and increased tumor growth.
Through experiments with murine models of breast cancer and melanoma, researchers found that estrogen signaling decreases the proliferation and survival of eosinophils by activating estrogen receptors (ER). This suppression not only lowers overall eosinophil numbers but also diminishes TATE prevalence, a factor correlated with weaker immune defenses in the tumor microenvironment. Remarkably, blocking ER signaling in these models halted tumor growth in an eosinophil-dependent manner, underscoring the critical role of eosinophils in controlling tumor spread.
The findings also indicated that combining ER inhibitors with ICB therapies could significantly improve immune response and reduce tumor growth. These results underscore the potential of integrating ER modulators with ICB therapies for a more robust approach against ER-positive breast cancers. Such combined therapies could potentially apply across various estrogen-sensitive tumors, providing new hope for patients whose cancer may otherwise evade immune detection due to estrogen’s suppressive effects on eosinophils.
Reference: Artham S et al. Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth. Sci Adv. 2024;10(9):eadp2442.
Anaya Malik | AMJ
