Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Oncoimmunology. 2021 Jun 28;10(1):1942673. doi: 10.1080/2162402X.2021.1942673. eCollection 2021.
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. TIGITTIM-3NK cells showed exhausted phenotypic characteristics and displayed dysfunction manifested as weakened killing function, reduced cytokine production, and proliferation function. TIGITTIM-3NK 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.
肝细胞癌 (HCC) 的预后极差，其中乙型肝炎病毒相关肝细胞癌 (HBV-HCC) 在中国占大多数。免疫检查点抑制剂已成为治疗 HCC 的一种有效免疫疗法，但它们主要用于 T 细胞。NK 细胞作为肿瘤的第一道防线起着至关重要的作用。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。HBV-HCC 患者 NK 细胞上 TIGIT 和 TIM-3 的共表达增加。TIGIT+TIM-3+NK 细胞表现出耗竭的表型特征，并表现出功能障碍，表现为杀伤功能减弱、细胞因子产生减少和增殖功能降低。TIGIT+TIM-3+NK 细胞参与 NK 细胞功能耗竭，与 HBV-HCC 患者的疾病进展密切相关，提示这是未来免疫治疗的一个新靶点。
