Endoplasmic reticulum stress induced LOX-1+CD15+ polymorphonuclear myeloid-derived suppressor cells in hepatocellular carcinoma
Endoplasmic reticulum stress induced LOX-1+CD15+ polymorphonuclear myeloid-derived suppressor cells in hepatocellular carcinoma
复制标题
内质网应激诱导肝细胞癌中 LOX-1 CD15 多形核骨髓源性抑制细胞
DOI：
10.1111/imm.12876
复制
发表时间：
2018-05-01
期刊：
影响因子：
6.4
通讯作者：
Li, Xing
中科院分区：
文献类型：
--
作者：
Nan, Jiang;Xing, Yan-Fang;Li, Xing
A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphisms myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven HCC patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included. LOX-1(+)CD15(+) PMN-MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases. LOX-1(+)CD15(+) PMN-MDSC in circulation were positively associated with those in HCC tissues. LOX-1(+)CD15(+) PMN-MDSCs significantly reduced proliferation and IFN- production of T cells with a dosage dependent manner with LOX-1(-)CD15(+) PMNs reached negative results. The suppression on T cell proliferation and IFN- production was reversed by ROS inhibitor and Arginase inhibitor. ROS level and activity of arginase of LOX-1(+)CD15(+) PMN were higher in LOX-1(+)CD15(+) PMN-MDSCs than LOX-1(-)CD15(+) PMNs, as well as the expression of the NADPH oxidase NOX2 and arginase I. RNA sequence revealed that LOX-1(+) CD15(+) PMN-MDSCs displayed significantly higher expression of spliced X-box -binding protein 1 (sXBP1), an endoplasmic reticulum (ER) stress marker. ER stress inducer induced LOX-1 expression and suppressive function for CD15(+) PMN from health donor. For HCC patients, LOX-1(+)CD15(+) PMN-MDSCs were positively related to overall survival. Above all, LOX-1(+)CD15(+) PMN-MDSC were elevated in HCC patients and suppressed T cell proliferation through ROS/Arg I pathway induced by ER stress. They presented positive association with the prognosis of HCC patients.
