TIGIT(+) TIM-3(+) NK cells are correlated with NK cell exhaustion and disease progression in patients with hepatitis B virus‑related hepatocellular carcinoma.
TIGIT(+) TIM-3(+) NK cells are correlated with NK cell exhaustion and disease progression in patients with hepatitis B virus‑related hepatocellular carcinoma.
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TIGIT TIM-3 NK 细胞与乙型肝炎病毒相关肝细胞癌患者的 NK 细胞耗竭和疾病进展相关
DOI：
10.1080/2162402x.2021.1942673
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发表时间：
2021
期刊：
影响因子：
7.2
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Yu L;Liu X;Wang X;Yan F;Wang P;Jiang Y;Du J;Yang Z
肝细胞癌（HCC）预后极差，其中B型肝炎病毒相关性肝细胞癌（HBV-HCC）在我国占绝大多数。免疫检查点抑制剂已成为治疗HCC的有效免疫治疗方法，但主要用于T细胞。NK细胞作为对抗肿瘤的第一道防线发挥着至关重要的作用。因此，我们探讨了HBV-HCC患者NK细胞上免疫检查点的特征性表达模式。我们分析了TIGIT和TIM-3的共表达与HBV-HCC患者临床进展的相关性。NK细胞上TIGIT和TIM-3的共表达在HBV-HCC患者中升高。TIGIT+TIM-3+NK细胞显示出衰竭的表型特征，并显示出表现为减弱的杀伤功能、减少的细胞因子产生和增殖功能的功能障碍。TIGIT+TIM-3+NK细胞参与NK细胞功能衰竭，与HBV-HCC患者的疾病进展密切相关，提示未来免疫治疗的新靶点。
The prognosis of hepatocellular carcinoma (HCC) is extremely poor, of which hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) accounts for the majority in China. Immune checkpoint inhibitors have become an effective immunotherapy method for the treatment of HCC, but they are mainly used for T cells. NK cells play a vital role as the first line of defense against tumors. Therefore, we explored the characteristic expression pattern of immune checkpoints on NK cells of HBV-HCC patients. We analyzed the correlation between the co-expression of TIGIT and TIM-3 and the clinical progress of patients with HBV-HCC. The co-expression of TIGIT and TIM-3 on NK cells is elevated in patients with HBV-HCC. TIGIT+TIM-3+NK cells showed exhausted phenotypic characteristics and displayed dysfunction manifested as weakened killing function, reduced cytokine production, and proliferation function. TIGIT+TIM-3+NK cells participate in NK cells function exhaustion and are closely related to the disease progression of patients with HBV-HCC, suggesting a new target for future immunotherapy.