Reduced Siglec-7 expression on NK cells predicts NK cell dysfunction in primary hepatocellular carcinoma.,Clinical & Experimental Immunology

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Reduced Siglec-7 expression on NK cells predicts NK cell dysfunction in primary hepatocellular carcinoma.
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-04-22 , DOI: 10.1111/cei.13444
L Tao ₁ , S Wang ₂ , L Yang ₃ , L Jiang ₃ , J Li ₄ , X Wang ₃

Affiliation

Major histocompatibility complex class I (MHC‐I)‐dependent inhibitory receptors on natural killer (NK) cells have been found to contribute to NK cell dysfunction in hepatocellular carcinoma (HCC). However, the roles of MHC‐I‐independent inhibitory receptors on NK cells in HCC remain poorly defined. In this study, we analyzed the expression of the MHC‐I‐independent inhibitory receptors sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐7 and Siglec‐9 on NK cells by analyzing the peripheral blood of 35 HCC patients and 63 healthy donors. We observed that HCC patients had lower frequencies and total numbers of NK cells in the peripheral blood. Importantly, both the expression levels of Siglec‐7 on NK cells and the frequencies of Siglec‐7⁺ NK cells were significantly reduced in HCC patients, which was accompanied by a decrease in activating receptor and an increase in inhibitory receptor expression on NK cells. Moreover, Siglec‐7⁺ NK cells expressed higher levels of activating receptors and displayed stronger effector functions, compared with Siglec‐7⁻ NK cells. Our findings demonstrate for the first time that reduced Siglec‐7 expression predicts NK cell dysfunction in HCC patients, suggesting that Siglec‐7 may be a potential marker of functional NK cell subset in HCC patients.

中文翻译：

NK 细胞上降低的 Siglec-7 表达可预测原发性肝细胞癌中的 NK 细胞功能障碍。

已发现自然杀伤 (NK) 细胞上的主要组织相容性复合体 I 类 (MHC-I) 依赖性抑制受体会导致肝细胞癌 (HCC) 中的 NK 细胞功能障碍。然而，MHC-I 非依赖性抑制性受体对 HCC NK 细胞的作用仍不清楚。在这项研究中，我们通过分析 35 名 HCC 患者和 63 名健康供体的外周血，分析了 MHC-I 非依赖性抑制受体唾液酸结合免疫球蛋白样凝集素 (Siglec)-7 和 Siglec-9 在 NK 细胞上的表达. 我们观察到 HCC 患者外周血 NK 细胞的频率和总数较低。重要的是，Siglec-7 在 NK 细胞上的表达水平和 Siglec-7 ⁺HCC 患者 NK 细胞显着减少，伴随着 NK 细胞上激活受体的减少和抑制性受体表达的增加。此外，与 Siglec-7 ^- NK 细胞相比，Siglec-7 ⁺ NK 细胞表达更高水平的激活受体并显示出更强的效应器功能。我们的研究结果首次证明，Siglec-7 表达降低可预测 HCC 患者的 NK 细胞功能障碍，表明 Siglec-7 可能是 HCC 患者功能性 NK 细胞亚群的潜在标志物。

更新日期：2020-04-22

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