Steroid hormone regulation of immune responses in cancer

Abstract

Steroid hormones are derived from cholesterol and can be classified into sex hormones (estrogens, androgens, progesterone) that are primarily synthesized in the gonads and adrenal hormones (glucocorticoids and mineralocorticoids) that are primarily synthesized in the adrenal gland. Although, it has long been known that steroid hormones have potent effects on the immune system, recent studies have led to renewed interest in their role in regulating anti-tumor immunity. Extra-glandular cells, such as epithelial cells and immune cells, have been shown to synthesize glucocorticoids and thereby modulate immune responses in the tumor microenvironment. Additionally, new insight into the role of androgens on immune cell responses have shed light on mechanisms underpinning the observed sex bias in cancer survival outcomes. Here, we review the role of steroid hormones, specifically glucocorticoids and androgens, in regulating anti-tumor immunity and discuss how their modulation could pave the way for designing novel therapeutic strategies to improve anti-tumor immune responses.