Viel Sébastien, Besson Laurie, Marotel Marie, Walzer Thierry, Marçais Antoine
Centre International de recherche en Infectiologie, CIRI, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, University of Lyon, 69007 Lyon, France.
Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, 69310 Pierre-Bénite, France.
Cancers (Basel). 2017 Sep 28;9(10):132. doi: 10.3390/cancers9100132.
The control of cellular metabolism is now recognized as key to regulate functional properties of immune effectors such as T or Natural Killer (NK) cells. During persistent infections or in the tumor microenvironment, multiple metabolic changes have been highlighted in T cells that contribute to their dysfunctional state or exhaustion. NK cells may also undergo major phenotypic and functional modifications when infiltrating tumors that could be linked to metabolic alterations. The mammalian target of rapamycin (mTOR) kinase is a central regulator of cellular metabolism. mTOR integrates various extrinsic growth or immune signals and modulates metabolic pathways to fulfill cellular bioenergetics needs. mTOR also regulates transcription and translation thereby adapting cellular pathways to the growth or activation signals that are received. Here, we review the role and regulation of mTOR in NK cells, with a special focus on cytokines that target mTOR such as IL-15 and TGF-β. We also discuss how NK cell metabolic activity could be enhanced or modulated to improve their effector anti-tumor functions in clinical settings.
细胞代谢的调控如今被认为是调节免疫效应细胞（如T细胞或自然杀伤细胞（NK细胞））功能特性的关键。在持续性感染或肿瘤微环境中，T细胞出现了多种代谢变化，这些变化导致其功能失调或耗竭。NK细胞浸润肿瘤时也可能发生主要的表型和功能改变，这可能与代谢改变有关。雷帕霉素的哺乳动物靶点（mTOR）激酶是细胞代谢的核心调节因子。mTOR整合各种外在生长或免疫信号，并调节代谢途径以满足细胞生物能量需求。mTOR还调节转录和翻译，从而使细胞途径适应所接收到的生长或激活信号。在此，我们综述mTOR在NK细胞中的作用和调控，特别关注靶向mTOR的细胞因子，如IL-15和TGF-β。我们还讨论了如何增强或调节NK细胞的代谢活性，以在临床环境中改善其抗肿瘤效应功能。
