Reduced CD160 Expression Contributes to Impaired NK-cell Function and Poor Clinical Outcomes in Patients with HCC

Cancer Research
Haoyu SunCheng Sun

Abstract

: We previously reported that deficiencies in natural killer (NK)-cell number and function play an important role in the progression of hepatocellular carcinoma (HCC). However, the mechanisms underlying this phenomenon remain obscure. In this study, we analyzed the expression of CD160 on intrahepatic NK cells by evaluating peritumoral and intratumoral tissues of 279 patients with HCC and 20 healthy livers. We observed reduced expression of CD160 on intratumoral NK cells, and patients with lower CD160 cell densities within tumor cells exhibited worse disease and a higher recurrence rate. High-resolution microarray and gene set enrichment analysis of flow cytometry-sorted primary intrahepatic CD160+ and CD160- NK cells of healthy livers indicated that human CD160+ NK cells exhibited functional activation, high IFNγ production, and NK-mediated immunity. In addition, global transcriptomic analysis of sorted peritumoral and intratumoral CD160+ NK cells revealed that intratumoral CD160+ NK cells are more exhausted than peritumoral CD160+ NK cells and produce less IFNγ. High levels of TGFβ1 interfered with production of IFNγ by CD160+ NK cells, blocking of which specifically restored IFNγ production in CD160+ NK cells to normal levels...Continue Reading

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Citations

Dec 4, 2019·Frontiers in Immunology·Meijuan Zheng, Zhigang Tian
Oct 13, 2020·Cellular & Molecular Immunology·Yongyan Chen, Zhigang Tian
Apr 6, 2021·Frontiers in Immunology·Julie GiraudMaya Saleh
Apr 9, 2021·Frontiers in Immunology·Gráinne Jameson, Mark W Robinson
Aug 11, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yuanyuan ZhengChuanyong Guo
Aug 28, 2021·International Journal of Molecular Sciences·Nicolas JacquelotPamela S Ohashi

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