Immunotherapy for targeting cancer stem cells in hepatocellular carcinoma.
Immunotherapy for targeting cancer stem cells in hepatocellular carcinoma.
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作者：
Dai X;Guo Y;Hu Y;Bao X;Zhu X;Fu Q;Zhang H;Tong Z;Liu L;Zheng Y;Zhao P;Fang W
检查点抑制剂的快速发展和显著成功为包括肝细胞癌在内的癌症治疗提供了重大突破。然而，只有15%-20%的肝癌患者可以从检查点抑制剂中受益。肿瘤干细胞(CSCs)在肝细胞癌的复发、转移以及局部和全身治疗抵抗中起重要作用。越来越多的证据表明，肝癌CSCs可以通过某些内在和外在机制创造免疫抑制微环境，从而导致免疫逃避。内在逃避机制主要包括免疫相关CSC信号通路的激活、抗原提呈分子的低水平表达和免疫抑制分子的高水平表达。外逃逸机制主要与乙肝病毒/丙型肝炎、酒精性/非酒精性脂肪性肝炎、低氧刺激、血管生成异常以及CSCs与免疫细胞之间的串扰有关。更好地了解CSCs参与免疫逃避的复杂机制将有助于肝癌的治疗。在这里，我们将概述CSCs免疫逃逸的详细机制，并提供目前针对CSCs的免疫治疗在肝细胞癌中的概述。
The rapid development and remarkable success of checkpoint inhibitors have provided significant breakthroughs in cancer treatment, including hepatocellular carcinoma (HCC). However, only 15-20% of HCC patients can benefit from checkpoint inhibitors. Cancer stem cells (CSCs) are responsible for recurrence, metastasis, and local and systemic therapy resistance in HCC. Accumulating evidence has suggested that HCC CSCs can create an immunosuppressive microenvironment through certain intrinsic and extrinsic mechanisms, resulting in immune evasion. Intrinsic evasion mechanisms mainly include activation of immune-related CSC signaling pathways, low-level expression of antigen presenting molecules, and high-level expression of immunosuppressive molecules. External evasion mechanisms are mainly related to HBV/HCV infection, alcoholic/nonalcoholic steatohepatitis, hypoxia stimulation, abnormal angiogenesis, and crosstalk between CSCs and immune cells. A better understanding of the complex mechanisms of CSCs involved in immune evasion will contribute to therapies for HCC. Here we will outline the detailed mechanisms of immune evasion for CSCs, and provide an overview of the current immunotherapies targeting CSCs in HCC.