Cancer Gene Therapy Unit, Division of Molecular Oncology, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy.
J Leukoc Biol. 2011 Oct;90(4):673-9. doi: 10.1189/jlb.0411198. Epub 2011 Jul 19.
The mechanisms of tumor immune evasion have gained increasing interest among the tumor immunologists, because of their ability to suppress spontaneous and immunotherapy-elicited antitumor responses. Recent studies clearly show that the deletion of cells/molecules involved in tumor evasion is capable of restoring antitumor immune responses, ultimately leading to tumor rejection in mouse tumor models. These studies further support and strengthen the idea to target not only the cancer cell-intrinsic defects but also those affecting cells of the microenvironment, such as immune cells. The alterations of cancer cell metabolism are also emerging as important regulators of immune cell function, with particular emphasis on immune-escape mechanisms. Indeed, intermediate or final products of cancer cell metabolism may interfere with the function of 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 migration to lymphoid organs, thus dampening the induction of successful antitumor responses. Finally, we will discuss whether this pathway may interfere with other immune cells infiltrating tumors and how to improve spontaneous and immunotherapy-based antitumor responses by counteracting this immune-escape mechanism.
肿瘤免疫学家越来越关注肿瘤免疫逃逸的机制，因为它们能够抑制自发和免疫疗法引起的抗肿瘤反应。最近的研究清楚地表明，删除参与肿瘤逃逸的细胞/分子能够恢复抗肿瘤免疫反应，最终导致小鼠肿瘤模型中的肿瘤排斥。这些研究进一步支持和加强了这样一种观点，即不仅要针对癌细胞内在的缺陷，还要针对影响微环境细胞（如免疫细胞）的缺陷。癌细胞代谢的改变也正在成为免疫细胞功能的重要调节剂，特别是在免疫逃逸机制方面。事实上，癌细胞代谢的中间或最终产物可能会干扰浸润肿瘤微环境的免疫细胞的功能。这篇综述将重点介绍胆固醇代谢的作用，特别强调 LXR/LXR 配体轴。该轴已被证明会影响 DC 向淋巴器官的迁移，从而抑制成功抗肿瘤反应的诱导。最后，我们将讨论该途径是否会干扰浸润肿瘤的其他免疫细胞，以及如何通过对抗这种免疫逃逸机制来改善自发和基于免疫疗法的抗肿瘤反应。
