线粒体片段化限制NK细胞肿瘤杀伤能力
2019-10-22 16:14
中国科学技术大学生命学院魏海明课题组和田志刚课题组合作揭示，线粒体片段化限制天然杀伤（NK）细胞介导的肿瘤免疫监控。相关论文2019年10月21日在线发表于《自然—免疫学》。
天然杀伤（NK）细胞在肿瘤监测中起关键作用。研究人员发现在人类肝癌中浸润肿瘤的NK细胞在其细胞质中具有小的、破碎的线粒体，而肿瘤外部的肝NK细胞以及周围的NK细胞具有正常的大的管状线粒体。这种片段化与降低的细胞毒性和NK细胞丢失相关，导致肿瘤逃避了NK细胞介导的监测，这预示着肝癌患者的生存率很低。
缺氧的肿瘤微环境驱使NK细胞中雷帕霉素-GTPase动力蛋白相关蛋白1（mTOR-Drp1）的机械靶标持续活化，导致线粒体过度分裂成碎片。线粒体片段化的抑制改善了线粒体的代谢、存活和NK细胞的抗肿瘤能力。这些数据揭示了一种免疫逃逸的机制，该机制可能是可靶向的，并且可以激发基于NK细胞的癌症治疗。
附：英文原文
Title:Mitochondrial fragmentation limits NK cell-based tumor immunosurveillance
Author:Xiaohu Zheng, Yeben Qian, Binqing Fu, Defeng Jiao, Yong Jiang, Peng Chen, Yiqing Shen, Huafeng Zhang, Rui Sun, Zhigang Tian & Haiming Wei
Issue&Volume: 21 October 2019
Abstract:
Natural killer (NK) cells have crucial roles in tumor surveillance. We found that tumor-infiltrating NK cells in human liver cancers had small, fragmented mitochondria in their cytoplasm, whereas liver NK cells outside tumors, as well as peripheral NK cells, had normal large, tubular mitochondria. This fragmentation was correlated with reduced cytotoxicity and NK cell loss, resulting in tumor evasion of NK cell-mediated surveillance, which predicted poor survival in patients with liver cancer. The hypoxic tumor microenvironment drove the sustained activation of mechanistic target of rapamycin-GTPase dynamin-related protein 1 (mTOR-Drp1) in NK cells, resulting in excessive mitochondrial fission into fragments. Inhibition of mitochondrial fragmentation improved mitochondrial metabolism, survival and the antitumor capacity of NK cells. These data reveal a mechanism of immune escape that might be targetable and could invigorate NK cell-based cancer treatments.
DOI:10.1038/s41590-019-0511-1
Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex
本期文章：《自然—免疫学》：Online/在线发表
