Cirrhosis is a high-risk state for hepatocellular carcinoma (HCC) development and represents an opportunity to prevent cancer. In the precancerous state of cirrhosis, there is an accumulation of neoantigens that may be specifically targetable through immunotherapy. We asked whether immune checkpoint inhibition could prevent tumorigenesis in a mouse model of diethylnitrosamine and carbon tetrachloride–induced HCC. We found that initiation of anti-PD-1 therapy prior to tumorigenesis could prevent up to 46% of liver tumors. This significant reduction in tumor burden was accompanied by infiltration of CD4+ Th cells and CD8+ cytotoxic T cells into the liver parenchyma. Importantly, anti-PD-1 therapy did not exacerbate liver dysfunction or worsen overall health in this liver disease model. Given the safety and preservation of quality of life observed with long-term immunotherapy use, an immunotherapy chemoprevention strategy is likely associated with a low risk-to-benefit ratio and high value care in select patients. These results encourage a prevention trial in cirrhotic patients with the highest risk of developing HCC. See related Spotlight by Mohammed et al., p. 897

中文翻译：

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免疫检查点抑制对肝细胞癌小鼠模型中的肝癌预防是安全有效的

肝硬化是肝细胞癌 (HCC) 发展的高风险状态，代表着预防癌症的机会。在肝硬化的癌前状态，新抗原的积累可能是通过免疫疗法特异性靶向的。我们询问免疫检查点抑制是否可以预防二乙基亚硝胺和四氯化碳诱导的 HCC 小鼠模型的肿瘤发生。我们发现在肿瘤发生之前开始抗 PD-1 治疗可以预防高达 46% 的肝脏肿瘤。这种肿瘤负荷的显着减少伴随着 CD4+ Th 细胞和 CD8+ 细胞毒性 T 细胞浸润到肝实质中。重要的是，在这种肝病模型中，抗 PD-1 治疗不会加剧肝功能障碍或恶化整体健康状况。鉴于长期使用免疫疗法观察到的安全性和生活质量的保持，免疫疗法化学预防策略可能与特定患者的低风险收益比和高价值护理相关。这些结果鼓励对发展为 HCC 的风险最高的肝硬化患者进行预防试验。参见 Mohammed 等人的相关 Spotlight，第 12 页。897