Detection and functional analysis of tumor-derived LXR ligands

There is growing evidence highlighting the ability of nuclear receptors to control not only metabolism, but also infl ammation and cancer progression. In particular liver X receptors (LXRs), the nuclear receptors physiologically involved in cholesterol homeostasis, have been shown to regulate innate and adaptive immune responses in many pathological conditions, including cancer. We have recently demonstrated that LXR ligands (oxysterols) released by tumor cells may have an immunomodulatory role, affecting the immune cells involved in the antitumor immune response. Indeed, oxysterols inhibit the expression of the chemokine receptor CCR7 on dendritic cells (DC) in an LXRdependent manner, thus impairing DC migration to secondary lymphoid organs, and therefore dampening the induction of successful antitumor responses. We have resorted to direct (i.e., luciferase-based LXR activation assay) and indirect (i.e., activation of LXR target genes in dendritic cells) methods in order to assess the presence of LXR ligands (oxysterols) in tumor-conditioned media. These two methods are also suitable to study strategies to block oxysterol release by tumor cells.