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Published on: November 15, 2013
LXR-dependent and -independent effects of oxysterols on immunity and tumor growth
Catia Traversari1, Silvano Sozzani, Knut R Steffensen
1Cancer Therapy, MolMed SpA, Milan, Italy.
Abstract:
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.
Insights
Oxysterols impact immune cells and tumor growth via liver X receptor (LXR)-dependent and -independent pathways. Understanding these mechanisms is crucial for developing new cancer therapies.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Oxysterols regulate cellular cholesterol homeostasis.
- Oxysterols modulate immune cell function and tumor progression.
- Oxysterol effects can be mediated by liver X receptors (LXRs) or independently.
Purpose of the Study:
- To review mechanisms linking oxysterols to tumor growth.
- To discuss LXR-dependent and -independent oxysterol effects on immune cells and tumor development.
Main Methods:
- Literature review of oxysterol-LXR signaling in cancer.
- Analysis of LXR isoform-specific effects (LXRα, LXRβ, LXRαβ).
- Examination of context-specific oxysterol actions in various pathologies.
Main Results:
- Oxysterol-LXR signaling can inhibit antitumor immune responses.
- Oxysterols influence tumor cell growth through LXR-dependent and -independent pathways.
- Isoform-specific LXR activation leads to transcriptional changes impacting cellular processes.
Conclusions:
- Oxysterols play a complex role in cancer immunity and tumor growth.
- LXR-dependent and -independent pathways offer distinct therapeutic targets.
- Further research is needed to elucidate specific networks and therapeutic potential.
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