Metabolism, LXR/LXR ligands, and tumor immune escape

The mechanisms of tumor immune evasion have gained increasing interest among the tumor immunologists, because of their ability to suppress spontaneous and immunotherapy-elicited antitumor responses. Recent studies clearly show that the deletion of cells/molecules involved in tumor evasion is capable of restoring antitumor immune responses, ultimately leading to tumor rejection in mouse tumor models. These studies further support and strengthen the idea to target not only the cancer cell-intrinsic defects but also those affecting cells of the microenvironment, such as immune cells. The alterations of cancer cell metabolism are also emerging as important regulators of immune cell function, with particular emphasis on immune-escape mechanisms. Indeed, intermediate or final products of cancer cell metabolism may interfere with the function of immune cells infiltrating the tumor microenvironment. This review will focus on the role of cholesterol metabolism, with particular emphasis on the axis LXR/LXR ligands. This axis has been shown to affect DC migration to lymphoid organs, thus dampening the induction of successful antitumor responses. Finally, we will discuss whether this pathway may interfere with other immune cells infiltrating tumors and how to improve spontaneous and immunotherapy-based antitumor responses by counteracting this immune-escape mechanism. J. Leukoc. Biol. 90: 673-679; 2011.