Abstract: The treatment of hepatocellular carcinoma (HCC) has witnessed radical changes over the last few years, with the introduction of immune checkpoint inhibitors (ICI) in clinical practice, namely the combination of atezolizumab plus bevacizumab as the standard of care for first-line treatment of advanced HCC. The immunosuppressive microenvironment of the chronically inflamed liver makes HCC a fertile ground for the use of ICI. This review focuses on anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAb), which have been extensively studied, as monotherapy, in combination with other ICI or with antiangiogenic agents. Currently, anti-PD-1 agents are approved by the United States Food and Drug Administration for second-line treatment in advanced HCC: nivolumab, alone or in combination with ipilimumab, and pembrolizumab. Lack of demonstration of survival benefit in first and second line led to the investigation of PD-1 agents in combination with multi-kinase inhibitors, with a number of first-line treatment regimens being actively investigated. Mounting evidence suggests a potential role of PD-1 blockade as adjuvant or neoadjuvant therapies. A key challenge remains the identification of biomarkers of response, since only a minority of patients appear to benefit from ICI.

Keywords: liver cancer, immunotherapy, advanced, immune checkpoint inhibition, PD-1, angiogenesis


中文翻译：

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PD-1 阻断肝细胞癌：当前研究和未来前景

摘要：肝细胞癌（HCC）的治疗在过去几年发生了根本性的变化，随着免疫检查点抑制剂（ICI）在临床实践中的引入，即阿特珠单抗联合贝伐珠单抗作为一线治疗的标准治疗高级肝细胞癌。慢性发炎肝脏的免疫抑制微环境使 HCC 成为使用 ICI 的沃土。本综述重点关注抗程序性细胞死亡 1 (PD-1) 单克隆抗体 (mAb)，已对其作为单一疗法、与其他 ICI 或抗血管生成剂联合使用进行了广泛研究。目前，美国食品和药物管理局批准抗 PD-1 药物用于晚期 HCC 的二线治疗：nivolumab，单独或与 ipilimumab 联合使用，以及 pembrolizumab。由于缺乏一线和二线生存获益的证明，因此对 PD-1 药物联合多激酶抑制剂进行了研究，并积极研究了许多一线治疗方案。越来越多的证据表明 PD-1 阻断剂作为辅助或新辅助治疗的潜在作用。一个关键的挑战仍然是识别反应的生物标志物，因为似乎只有少数患者从 ICI 中受益。

关键词：肝癌，免疫治疗，晚期，免疫检查点抑制，PD-1，血管生成