IL-6-induced CD39 expression on tumor-infiltrating NK cells predicts poor prognosis in esophageal squamous cell carcinoma
IL-6-induced CD39 expression on tumor-infiltrating NK cells predicts poor prognosis in esophageal squamous cell carcinoma
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IL-6诱导的肿瘤浸润NK细胞上的CD39表达预示着食管鳞状细胞癌的不良预后
DOI：
10.1007/s00262-020-02629-1
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发表时间：
2020-06-10
影响因子：
5.8
通讯作者：
Huang, Lan
中科院分区：
文献类型：
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作者：
Zheng, Yujia;Li, Yu;Huang, Lan
自然杀伤（NK）细胞是一种主要的先天性淋巴细胞亚群，介导恶性细胞的根除。外核苷酸酶CD 39介导的嘌呤能信号传导可抑制肿瘤中的T细胞应答。然而，CD 39在NK细胞中的作用尚未完全阐明。在这里，我们的特点CD 39的NK细胞的表达及其在食管鳞状细胞癌（ESCC）的临床意义。收集36例ESCC患者的外周血和组织样本。我们观察到，与配对外周血相比，ESCC患者癌组织中NK细胞的比例显著降低，但CD 39明显上调。此外，具有高CD 39表达的肿瘤浸润NK细胞表现出功能受损的表型。在体外，ESCC细胞系的条件培养基可以诱导来自健康供体的外周NK细胞表达CD 39。IL-6被鉴定为ESCC细胞系产生的主要细胞因子，并且在ESCC患者的肿瘤组织和血清中也升高。重组IL-6显著诱导人NK细胞表面CD 39表达，而IL-6受体拮抗剂托珠单抗阻止了这种作用。最后，肿瘤浸润性CD 39 +NK细胞与ESCC患者的不良预后相关。因此，肿瘤来源的IL-6可能通过诱导CD 39表达而损害NK细胞功能。CD 39 +NK细胞可能作为ESCC患者的潜在预后生物标志物。
Natural killer (NK) cells, a predominant innate lymphocyte subset, mediates eradicating malignant cells. Purinergic signaling by ectonucleotidase CD39 can suppress T-cell response in caner. However, the role of CD39 in NK cells has not been fully elucidated. Here, we characterized CD39 expression on NK cells and its clinical relevance in esophageal squamous cell carcinoma (ESCC). Peripheral blood and tissue samples were collected from 36 ESCC patients. We observed that the proportion of NK cells significantly decreased but CD39 was obviously up-regulated on NK cells from cancerous tissues compared to paired peripheral blood in ESCC patients. Furthermore, tumor-infiltrating NK cells with high CD39 expression exhibited a phenotype of functional impairment. In vitro, conditioned media of ESCC cell lines could induce CD39 expression on peripheral NK cells from healthy donors. IL-6 was identified as the major cytokine produced by ESCC cell lines and also elevated in both tumor tissues and blood serum from ESCC patients. Recombinant IL-6 significantly induced surface CD39 expression in human NK cells, while IL-6-receptor antagonist tocilizumab prevented this effect. Finally, tumor-infiltrating CD39+NK cells were correlated with poor prognosis in ESCC patients. Thus, tumor-derived IL-6 might impair NK cell functions through induction of CD39 expression. CD39+NK cells may serve as a potential prognostic biomarker for ESCC patients.