Accumulation of Tumor-Infiltrating CD49a+ NK Cells Correlates with Poor Prognosis for Human Hepatocellular Carcinoma
Accumulation of Tumor-Infiltrating CD49a+ NK Cells Correlates with Poor Prognosis for Human Hepatocellular Carcinoma
复制标题
肿瘤浸润性 CD49a( ) NK 细胞的积累与人肝细胞癌的不良预后相关
DOI：
10.1158/2326-6066.cir-18-0757
复制
发表时间：
2019-09-01
影响因子：
10.1
通讯作者：
Sun, Cheng
中科院分区：
文献类型：
--
作者：
Sun, Haoyu;Liu, Lianxin;Sun, Cheng
在小鼠中发现CD 49 a（+）肝脏驻留的自然杀伤（NK）细胞改变了我们对NK细胞的看法，并提供了另一个研究NK细胞的机会。虽然有证据表明NK细胞在肝脏疾病中的作用，但CD 49 a（+）NK细胞是否以及如何导致肝脏疾病仍不清楚。在这项研究中，我们观察到CD 49 a（+）组织驻留NK细胞在人肝细胞癌（HCC）中的积累高于癌周组织。我们通过蛋白质和mRNA分析研究了CD 49 a（+）组织驻留NK细胞的耗竭和调节表型。CD 49 a（+）NK细胞比例与表达抑制性受体的NK细胞比例呈正相关。此外，CD 49 a（+）NK细胞表达更多的检查点分子PD-1、CD 96和TIGIT。转录组学分析表明CD 49 a（+）组织驻留NK细胞参与了免疫反应的负调节。小鼠和人CD 49 a（+）NK细胞的比较揭示了它们不同的特性和功能。最后，肝肿瘤中组织驻留的CD 49 a（+）NK细胞的积累与病情恶化和预后不良相关。我们的研究结果表明，CD 49 a（+）NK细胞在肝肿瘤中积聚，并提示CD 49 a（+）NK细胞在免疫应答的负调节和HCC的发展中起作用。
The discovery of CD49a(+) liver-resident natural killer (NK) cells in mice alters our view of NK cells and provides another opportunity to study NK cells. Although evidence has suggested roles for NK cells in liver diseases, whether and how CD49a(+) NK cells contribute to liver diseases remain unclear. In this study, we observed that accumulation of CD49a(+) tissue-resident NK cells in human hepatocellular carcinoma (HCC) was higher than in peritumoral tissues. We studied the exhausted and regulatory phenotypes of CD49a(+) tissue-resident NK cells by analysis of protein and mRNA. The proportion of CD49a(+) NK cells was positively correlated to the proportion of NK cells expressing inhibitory receptors. In addition, CD49a(+) NK cells expressed more of checkpoint molecules PD-1, CD96, and TIGIT. Transcriptomic analysis implicated CD49a(+) tissue-resident NK cells in the negative regulation of immune responses. Comparison of murine and human CD49a(+) NK cells revealed their distinct characteristics and functions. Finally, accumulation of tissue-resident CD49a(+) NK cells in liver tumor was correlated to deteriorating disease condition and poor prognosis. Our findings show that CD49a(+) NK cells accumulate in liver tumor and suggest a role for CD49a(+) NK cells in the negative regulation of immune responses and the development of HCC.