Department for Immunology, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), D-44139 Dortmund, Germany.
Institute for Virology, University Hospital Essen, D-45147 Essen, Germany.
Cells. 2022 Nov 3;11(21):3489. doi: 10.3390/cells11213489.
Tumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the effect of Glutor, an inhibitor of glucose transporters, on the function of human Natural Killer (NK) cells, which are important for the immunosurveillance of cancer. Glutor treatment effectively inhibits glycolysis in NK cells. However, acute treatment with the inhibitor has no effect on NK cell effector functions. Prolonged inhibition of glucose uptake by Glutor prevents the proliferation of NK cells, increases their pro-inflammatory regulatory function and reduces the stimulation-dependent production of IFN-γ. Interestingly, even after prolonged Glutor treatment NK cell cytotoxicity and serial killing activity were still intact, demonstrating that cytotoxic NK cell effector functions are remarkably robust against metabolic disturbances.
肿瘤细胞通常有很高的能量需求。因此，抑制葡萄糖摄取可能是限制转化细胞增殖和存活的一种方法。然而，免疫细胞也需要能量来启动和维持抗肿瘤免疫反应。在这里，我们研究了 Glutor（一种葡萄糖转运蛋白抑制剂）对人自然杀伤 (NK) 细胞功能的影响，NK 细胞对于癌症的免疫监视很重要。Glutor 处理可有效抑制 NK 细胞的糖酵解。然而，抑制剂的急性处理对 NK 细胞效应功能没有影响。Glutor 长时间抑制葡萄糖摄取可阻止 NK 细胞增殖，增加其促炎调节功能，并减少刺激依赖性 IFN-γ的产生。有趣的是，即使经过长时间的 Glutor 处理，NK 细胞的细胞毒性和连续杀伤活性仍然完整，这表明细胞毒性 NK 细胞的效应功能对代谢紊乱具有很强的耐受性。
