Immunopathology Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.
Basque Foundation for Science, Bilbao, Spain.
Sci Rep. 2021 Mar 19;11(1):6472. doi: 10.1038/s41598-021-85960-6.
Natural Killer (NK) cells acquire memory-like properties following a brief stimulation with IL-12, IL-15 and IL-18. These IL-12/15/18-preactivated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have been revealed as a powerful tool in cancer immunotherapy due to their persistence in the host and their increased effector functions. Several studies have shown that NK cells modulate their metabolism in response to cytokine-stimulation and other stimuli, suggesting that there is a link between metabolism and cellular functions. In this paper, we have analyzed metabolic changes associated to IL-12/15/18-stimulation and the relevance of glycolytic pathway for NK cell effector functions. We have found CIML NK cells are able to retain a metabolic profile shifted towards glycolysis seven days after cytokine withdrawal. Furthermore, we found that treatment with 2-DG differently affects distinct NK cell effector functions and is stimuli-dependent. These findings may have implications in the design of NK cell-based cancer immunotherapies.
自然杀伤 (NK) 细胞在接受短暂的白细胞介素-12 (IL-12)、白细胞介素-15 (IL-15) 和白细胞介素-18 (IL-18) 刺激后获得记忆样特性。这些被称为细胞因子诱导的记忆样 (CIML) NK 细胞的 IL-12/15/18 预激活 NK 细胞，由于其在宿主中的持久性和增强的效应功能，已被证明是癌症免疫治疗的有力工具。多项研究表明，NK 细胞会根据细胞因子刺激和其他刺激来调节其代谢，这表明代谢与细胞功能之间存在联系。在本文中，我们分析了与 IL-12/15/18 刺激相关的代谢变化，以及糖酵解途径对 NK 细胞效应功能的相关性。我们发现，CIML NK 细胞能够在细胞因子撤去七天后保留向糖酵解转移的代谢特征。此外，我们发现，2-DG 的处理以不同的方式影响不同的 NK 细胞效应功能，并且依赖于刺激。这些发现可能对基于 NK 细胞的癌症免疫疗法的设计具有重要意义。
