The imbalance of NKG2A and NKG2D expression is involved in NK cell immunosuppression and tumor progression of HBV‐HCC patients
The imbalance of NKG2A and NKG2D expression is involved in NK cell immunosuppression and tumor progression of HBV‐HCC patients
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NKG2A和NKG2D表达失衡参与HBV-HCC患者NK细胞免疫抑制和肿瘤进展
DOI：
10.1111/hepr.13877
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发表时间：
2023
影响因子：
4.2
通讯作者：
Zhiyun Yang
中科院分区：
文献类型：
--
作者：
Lihua Yu;Lei Sun;Xiaoli Liu;Xinhui Wang;Huiwen Yan;Qing Pu;Yuqing Xie;Yuyong Jiang;Juan Du;Zhiyun Yang
背景肿瘤微环境中的免疫抑制与肿瘤的进展有关。自然杀伤组2（NKG 2）家族蛋白，包括抑制性受体和激活剂，可用作免疫检查点抑制的免疫治疗的有吸引力的靶标。我们进一步探讨NKG 2A和NKG 2D的表达水平在B型肝炎病毒相关肝细胞癌（HBV-HCC）中的预后价值。MethodsThis study was a prospective study involving 92例HBV-HCC患者，16例HBV相关肝硬化患者，18例CH B患者，38例健康供体。我们分析了HBV‐HCC患者外周血中NKG 2A、NKG 2D的表达和相关功能以及NKG 2A/NKG 2D比值，并分析了肿瘤进展。结果在肿瘤进展的HBV-HCC患者中，NK细胞和T细胞中NKG 2A/NKG 2D的比例较高。Kaplan-Meier生存曲线显示，NK细胞上的NKG 2A/NKG 2D比值可预测HBV‐HCC患者的肿瘤进展，该比值的增加与NK细胞功能抑制相关。结论NK细胞NKG 2A/NKG 2D比例失衡参与NK细胞免疫抑制，NKG 2A/NKG 2D比例升高与HBV-HCC的肿瘤进展有关。
BackgroundImmunosuppression in a tumor microenvironment is associated with enhanced tumor progression. Natural killer group 2 (NKG2) family proteins, including inhibitory receptors and activators, can be used as attractive targets for immunotherapy of immune checkpoint inhibition. We further explore the expression level prognostic value of NKG2A and NKG2D in hepatitis B virus‐related hepatocellular carcinoma (HBV‐HCC).MethodsThis study was a prospective study involving 92 patients with HBV‐HCC, 16 patients with HBV‐related liver cirrhosis, 18 patients with CHB, and 38 healthy donors. We analyzed the expression and related functions of NKG2A, NKG2D, and the NKG2A/NKG2D ratio in the peripheral blood of patients with HBV‐HCC and analyzed tumor progression. The tissue samples from patients with HBV‐HCC were further used for multiple immunofluorescence and immunohistochemistry.ResultsIn patients with HBV‐HCC with tumor progression, the ratio of NKG2A/NKG2D is higher in NK cells and T cells. The Kaplan–Meier survival curve showed that the NKG2A/NKG2D ratio on NK cells could predict tumor progression in patients with HBV‐HCC, and that an increase in this ratio was associated with inhibition of NK cell function. The Cancer Genome Atlas (TCGA) database was further used to verify that the higher the NKG2A/NKG2D ratio, the shorter the progression‐free survival of patients with HCC, and the more likely the immune function was suppressed.ConclusionsThe imbalance between NKG2A and NKG2D of NK cells is involved in NK cell immunosuppression, and the increase of the NKG2A/NKG2D ratio is related to the tumor progression of HBV‐HCC.