Comprehensive characterization of tumor infiltrating natural killer cells and clinical significance in hepatocellular carcinoma based on gene expression profiles

•The relative abundance of NK cells is lower in HCC than adjacent normal tissues.•The HCC subclasses showed distinct NK scores and expression patterns of NK-specific gene signatures.•The receptor-ligand pairs of immune checkpoint genes may be the major cause of immune evasion and immunotherapeutic t...

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Veröffentlicht in:Biomedicine & pharmacotherapy 2020-01, Vol.121, p.109637-109637, Article 109637
Hauptverfasser: Wu, Mei, Mei, Fang, Liu, Weishuo, Jiang, Jianwei
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Sprache:eng
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Zusammenfassung:•The relative abundance of NK cells is lower in HCC than adjacent normal tissues.•The HCC subclasses showed distinct NK scores and expression patterns of NK-specific gene signatures.•The receptor-ligand pairs of immune checkpoint genes may be the major cause of immune evasion and immunotherapeutic targets.•Higher NK scores may be an indicator of sorafinib response and favorable prognosis. Natural Killer (NK) cells are effector lymphocytes involved in tumor immunosurveillance, however, the specific mechanism in hepatocellular carcinoma (HCC) has not been well understood. In the present study, we estimated the relative abundances of NK cells in HCC using gene expression data, and found that NK cell abundance was lower in HCC tissues than in the adjacent normal tissues. With the common HCC subclasses, we also found that three HCC subclasses had distinct abundances of NK cells. Moreover, we also found strong association between NK cell abundances and genes encoding immune checkpoint proteins, such as KLRD1, CD96, TIGIT, CD86, HAVCR2, PDCD1 (PD-1), HLA-E, CD274 (PD-L1), and CTLA4, among which, KLRD1 vs. HLA-E, CD274 vs. PDCD1, and CTLA4 vs. CD86 were three pairs of receptors and ligands. Furthermore, we investigated the clinical significance of NK cell activities in HCC, and found that the NK cell abundances were highly associated with the response to sorafinib, and higher NK cell abundances may prolong both the recurrence-free and overall survival of HCC patients. In summary, the present study not only improved our understanding of the potential tumor immune evasion mechanism of NK cells in HCC, but also proposed the potential clinical application of NK activities in HCC treatment and risk assessment.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2019.109637