Cancer Therapy, MolMed SpA, Milan, Italy.
Eur J Immunol. 2014 Jul;44(7):1896-903. doi: 10.1002/eji.201344292. Epub 2014 May 22.
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.
氧化固醇参与维持细胞内胆固醇水平。最近，氧化固醇被证明可以调节免疫细胞的功能和肿瘤生长。这些作用可能依赖于氧化固醇结合肝 X 受体（LXRs）的激活，或者如最近在 T 和 B 细胞、DC 和中性粒细胞中所证明的那样，不依赖于 LXR 激活。LXR 依赖性氧化固醇作用可归因于 LXRα、LXRβ 或 LXRαβ 同工型的激活，其诱导靶基因的转录激活或反式阻遏。一种同工型的普遍激活似乎是细胞、组织或上下文特异性的，如在某些病理过程中，即传染病、动脉粥样硬化和自身免疫中所示。氧化固醇-LXR 信号最近被证明抑制抗肿瘤免疫反应，并调节肿瘤细胞生长。在这里，我们综述了将氧化固醇与肿瘤生长联系起来的机制，并讨论了 LXR 依赖性和非依赖性氧化固醇对免疫细胞和肿瘤发展的影响的基础上可能存在的网络。
