Cell Metabolism丨魏海明/田志刚合作组揭示NK细胞丧失抗肿瘤功能背后的代谢调控过程

2018年8月Cell Metabolism以封面故事文章的形式发表了中国科学技术大学生命科学与医学部、中科院天然免疫与慢性疾病重点实验室和合肥微尺度物质科学国家研究中心魏海明教授和田志刚教授课题组合作研究的论文Dysfunction of Natural Killer Cells by FBP1-induced Inhibition of Glycolysis during Lung Cancer Progression，该项研究成果展示了肿瘤发生发展过程中自然杀伤细胞（NK细胞）的动态改变，并从糖代谢调控的角度揭示了一种NK细胞功能紊乱的新机制。

设计者：陈磊、王国燕

封面图像链接  https://www.cell.com/cell-metabolism/current

On the cover: Lung cancer poses a high mortality rate, but more advanced therapeutics, such as immunotherapy, hold promise in ameliorating this common disease. Natural killer (NK) cells, cytotoxic innate immune cells, have established roles in resisting numerous tumor types, but little is known about their function in lung cancer development. Herein, Cong et al. (pp. 243–255) utilize a Kras-driven model of spontaneous lung cancer to investigate the state of NK cells at different stages of tumor development. They find NK cells gradually enter a dysfunctional state, losing their antitumor effect as aberrant fructose-1,6-bisphosphatase (FBP1) expression inhibits glycolysis and impairs viability. The work suggests new directions for NK cell-based cancer immunotherapy involving FBP1 targeting. The cover image illustrates the tragic story of warriors (NK cells) of a concentric castle, fighting against the enemy (cancer cells) but progressively losing their defense at each castle wall, representing the stages of tumor development: initiation, promotion, and progression. Cover art by Lei Chen and Guoyan Wang, USTC.

自然杀伤细胞 (natural killer cell，NK细胞) 是一种效应淋巴细胞，在机体抵抗肿瘤过程中发挥至关重要的作用。NK细胞无需预先致敏，即能够直接杀伤肿瘤细胞，并且能够通过分泌细胞因子促进适应性免疫的抗肿瘤作用【1】。基于上述原理，NK细胞在肿瘤免疫治疗中的价值已得到广泛认可【2】。然而，越来越多的研究表明，肿瘤生长过程中，肿瘤细胞可以通过多种机制诱导NK细胞功能紊乱，从而逃避NK细胞的监视，这主要是由于肿瘤细胞分泌的转化生长因子-β (TGF-β) 、前列腺素E2 (prostaglandin, PGE2) 和IL-10等因素造成的【3】。肿瘤发生发展是一个漫长的过程，主要包括起始期、促进期和进展期三个阶段，然而在这整个过程中，NK细胞与肿瘤细胞如何相互作用仍不得而知。

近几年来，代谢调控在肿瘤、免疫、表观遗传等领域越来越受重视，对于NK细胞来说相关的代谢研究较少，目前主要集中在糖代谢调控与NK细胞功能方面【4-6】。然而糖代谢的变化与NK细胞在肿瘤中的效应功能相关的而研究目前并不清楚。

为了最大可能被采用，我们之前还做过一个这样色调的版本：