Metabolism, LXR/LXR ligands, and tumor immune escape

The mechanisms of tumor immune evasion have gainedincreasing interest among the tumor immunologists,because of their ability to suppress spontaneous andimmunotherapy-elicited antitumor responses. Recentstudies clearly show that the deletion of cells/moleculesinvolved in tumor evasion is capable of restoringantitumor immune responses, ultimately leading to tumorrejection in mouse tumor models. These studiesfurther support and strengthen the idea to target notonly the cancer cell-intrinsic defects but also those affectingcells of the microenvironment, such as immunecells. The alterations of cancer cell metabolism are alsoemerging as important regulators of immune cell function,with particular emphasis on immune-escapemechanisms. Indeed, intermediate or final products ofcancer cell metabolism may interfere with the functionof 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 migrationto lymphoid organs, thus dampening the induction ofsuccessful antitumor responses. Finally, we will discusswhether this pathway may interfere with other immunecells infiltrating tumors and how to improve spontaneousand immunotherapy-based antitumor responses bycounteracting this immune-escape mechanism. © Society for Leukocyte Biology.