Mitochondrion is the center of cell metabolism, its morphology is highly dynamic, and it continuously fuses and divides. After mitochondrion fusion, it is linear or tubular, and its respiration and oxidative phosphorylation are strengthened. It could also interact with endoplasmic reticulum to improve the flow of calcium ions and play a normal function of cells. After mitosis, ROS production, apoptosis and autophagy would be accelerated, which will seriously interfere with the normal function of cells.
By using transmission electron microscopy, researchers could clearly see the significant difference between normal and tumor infiltrated NK cells. The normal NK cell’s mitochondria is tubular and large, while the one of tumor infiltrated NK cell is fragmented and small. Further study on its mechanism showed that the hypoxia state of tumor microenvironment was an important reason for inducing mitochondrial rupture of NK cells; hypoxia could continuously activate signal of NK cells in tumor microenvironment, leading to excessive mitosis of mitochondria, resulting in decreased NK cell’s activity and tumor killing ability. In the patients with liver cancer, the more serious the local hypoxia is, the less the number of NK infiltrated cells in tumor tissue is, which tends to be cold tumor, and the survival period of patients is worse. After pretreatment with mTOR or inhibitors, the mitochondrial morphology and respiratory effect of NK cells in tumor microenvironment were significantly improved, and the tumor killing ability was also enhanced.
This study explains the new mechanism of tumor derived NK cells' function disorder and immune escape from the perspective of metabolism, and provides a new strategy for improving the immunotherapy of NK cells.
(Written by YANG Xinqi, edited by LI Xiaoxi, materials provided by Life Sciences and Medical Department of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, HFNL-Microscale and Scientific Research Department.)
On May 11, the Nature Publishing Group released Nature Publishing Index 2010 China, remarking “a dramatic rise in the quality of research being published by China”. University of Science and Technology of China is ranked 3rd of TOP 10 Institutions in Index 2010 China.
This article came from News Center of USTC.