Cholesterol plays an indispensable role in regulating the properties of cell membranes in mammalian cells. Accumulation of
cholesterol and its intermediates, such as
oxysterols, lead to activation of the
nuclear receptors LXRs (
liver X receptors). LXR is an important regulator of
cholesterol homoeostasis by controlling its transport and its neo-synthesis. Accumulating evidence indicates that the endogenous
ligands of LXRs,
oxysterols, play an active and important role in regulating the fate and function of immune cells. Indeed, LXRs are negative regu-lators of innate immunity by interfering with macrophage activation. Recent advances have highlighted a controversial role for LXR in
cancer. In this issue of the Biochemical Journal, Wang et al. propose that LXR agonist directly controls IFN-γ (
interferon-γ) expression, which limits tumour growth. This protective effect mediated by LXR appears to be dependent on IFN-γ. Thus, despite accumulation of endogenous
ligand of LXR in
cancer, activation of LXR seems protective. This novel evidence provides a new perspective for targeting LXR in
cancer, although controversial studies can be also found in the literature. In order to avoid side effects associated with LXR agonists, molecular and cellular studies are required to decipher this unexpected action of LXRs.