LXR-dependent and -independent effects of oxysterols on immunity and tumor growth.
Oxysterols are involved in maintaining cellular cholesterol levels. Recently, oxysterols have been demonstrated to modulate the function of immune cells and tumor growth. These effects can be dependent on the activation of the oxysterol-binding liver X receptors (LXRs) or, as recently demonstrated for T and B cells, DCs and neutrophils, can be independent of LXR activation. LXR-dependent oxysterol effects can be ascribed to the activation of LXRα, LXRβ or LXRαβ isoforms, which induces transcriptional activation or trans-repression of target genes. The prevalent activation of one isoform seems to be cell-, tissue-, or context-specific, as shown in some pathologic processes, i.e., infectious diseases, atherosclerosis, and autoimmunity. Oxysterol-LXR signaling has recently been shown to inhibit antitumor immune responses, as well as to modulate tumor cell growth. Here, we review the mechanisms that link oxysterols to tumor growth, and discuss possible networks at the basis of LXR-dependent and -independent oxysterol effects on immune cells and tumor development.
Cancer Therapy, MolMed SpA, Milan, Italy.
Catia
C
Traversari
Silvano
S
Sozzani
Knut R
KR
Steffensen
Vincenzo
V
Russo
D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D007109:Immunity; D000071518:Liver X Receptors; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D009369:Neoplasms / Q000473:pathology*; D057093:Orphan Nuclear Receptors / Q000502:physiology*; D054400:Receptors, CCR7 / Q000502:physiology; D059016:Tumor Microenvironment
D006888:Hydroxycholesterols; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D054400:Receptors, CCR7; D002784:Cholesterol
Antitumor immune responses; Liver X receptor(s); Oxysterols