School of Basic Medical Sciences and Women's Hospital, Zhejiang University School of Medicine; Cancer Center, Zhejiang University, Hangzhou, China.
Adv Exp Med Biol. 2021;1316:71-85. doi: 10.1007/978-981-33-6785-2_5.
Accumulative data demonstrate that during the initiation and progression of tumors, several types of cellular components in tumor microenvironment, including tumor cells and immune cells, exhibit malfunctions in cellular energy metabolism. For instance, lipid metabolism impairments in immune cells are crucial in coordinating immunosuppression and tumor immune escape. In particular, excessive lipids have been shown to exhibit negative effects on innate immunity. Previous studies on lipid metabolism in immune cells are mainly focused on macrophages and T lymphocytes. Although natural killer (NK) cells are major players in the innate elimination of virus, bacteria, and tumor cells, available literature reports related with lipid metabolism in NK cells and tumor-associated NK (TANK) cells are very sparse. Despite these, the importance and clinical relevance of the crosstalk among lipid metabolism, NK/TANK cells, and tumors have been clearly indicated. In this chapter, following a general description of NK and TANK cells, our knowledge on the regulation of lipid metabolism in NK cells is reviewed, with an emphasis on the roles of mTOR and SREBP signaling. Then the interactions between lipid metabolism and NK/TANK cells under pathological conditions, e.g., obesity and cancer, were carefully introduced. As there is an urgent need to reveal more regulators and to clarify detailed molecular mechanisms by which lipid metabolism interacts with NK/TANK cells, several categories of potential regulators/pathways, as well as the challenges and perspectives in this emerging field, are discussed.
积累的数据表明,在肿瘤的发生和发展过程中,肿瘤微环境中的几种细胞成分,包括肿瘤细胞和免疫细胞,其细胞能量代谢出现功能障碍。例如,免疫细胞中的脂质代谢损伤对于协调免疫抑制和肿瘤免疫逃逸至关重要。特别是,过多的脂质对先天免疫表现出负面影响。目前关于免疫细胞中脂质代谢的研究主要集中在巨噬细胞和 T 淋巴细胞上。虽然自然杀伤 (NK) 细胞是先天消除病毒、细菌和肿瘤细胞的主要参与者,但与 NK 细胞和肿瘤相关 NK (TANK) 细胞中的脂质代谢相关的可用文献报道非常稀少。尽管如此,脂质代谢、NK/TANK 细胞和肿瘤之间的串扰的重要性和临床相关性已经得到明确表明。在本章中,在对 NK 和 TANK 细胞进行一般性描述之后,我们回顾了 NK 细胞中脂质代谢的调控知识,重点介绍了 mTOR 和 SREBP 信号通路的作用。然后仔细介绍了在肥胖和癌症等病理条件下,脂质代谢与 NK/TANK 细胞之间的相互作用。由于迫切需要揭示更多的调控因子,并阐明脂质代谢与 NK/TANK 细胞相互作用的详细分子机制,因此讨论了几类潜在的调控因子/通路,以及该新兴领域面临的挑战和前景。