title: Cholesterol metabolites and tumor microenvironment: the road towards clinical translation.
abstract: Targeting the tumor microenvironment focusing on immune cells has recently become a standard of care for some tumors. Indeed, antibodies blocking immune checkpoints (e.g., anti-CTLA-4 and anti-PD1 mAbs) have been approved by regulatory agencies for the treatment of some solid tumors based upon successes in many clinical trials. Although tumor metabolism has always attracted the attention of tumor biologists, only recently have oncologists renewed their interest in this field of tumor biology research. This has highlighted the possibility to pharmacologically target rate-limiting enzymes along key metabolic pathways of tumor cells, such as lipogenesis and aerobic glycolysis. Altered tumor metabolism has also been shown to influence the functionality of the tumor microenvironment as a whole, particularly the immune cell component of thereof. Cholesterol, oxysterols and Liver X receptors (LXRs) have been investigated in different tumor models. Recent in vitro and in vivo results point to their involvement in tumor and immune cell biology, thus making the LXR/oxysterol axis a possible target for novel antitumor strategies. Indeed, the possibility to target both tumor cell metabolism (i.e., cholesterol metabolism) and tumor-infiltrating immune cell dysfunctions induced by oxysterols might result in a synergistic antitumor effect generating long-lasting memory responses. This review will focus on the role of cholesterol metabolism with particular emphasis on the role of the LXR/oxysterol axis in the tumor microenvironment, discussing mechanisms of action, pros and cons, and strategies to develop antitumor therapies based on the modulation of this axis.
authors.affiliation: Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, Division of Experimental Oncology, San Raffaele Scientific Institute, via Olgettina 58, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Raccosta
authors.affiliation: Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, Division of Experimental Oncology, San Raffaele Scientific Institute, via Olgettina 58, Milan, Italy.|San Raffaele Vita-Salute University, via Olgettina 60, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Fontana
authors.affiliation: Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, Division of Experimental Oncology, San Raffaele Scientific Institute, via Olgettina 58, Milan, Italy.
authors.forename: Gianfranca
authors.initials: G
authors.lastname: Corna
authors.affiliation: Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, Division of Experimental Oncology, San Raffaele Scientific Institute, via Olgettina 58, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Maggioni
authors.affiliation: Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, Division of Experimental Oncology, San Raffaele Scientific Institute, via Olgettina 58, Milan, Italy.|San Raffaele Vita-Salute University, via Olgettina 60, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Moresco
authors.affiliation: Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, Division of Experimental Oncology, San Raffaele Scientific Institute, via Olgettina 58, Milan, Italy. v.russo@hsr.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Russo
mesh_terms: D002784:Cholesterol / Q000276:immunology*; D006801:Humans; D059016:Tumor Microenvironment
chemical_list: D002784:Cholesterol
keywords: Immune cells; Immunotherapy; Metabolism; Microenvironment; NIBIT 2014; Tumor