索拉非尼
医学
免疫疗法
肝细胞癌
内科学
肿瘤科
联合疗法
抗体
危险系数
无容量
免疫检查点
靶向治疗
CD8型
封锁
免疫学
免疫系统
癌症研究
胃肠病学
置信区间
癌症
受体
作者
Hiroto Kikuchi,Aya Matsui,Satoru Morita,Zohreh Amoozgar,Koetsu Inoue,Zhiping Ruan,Daniel Staiculescu,Jeffrey Sum-Lung Wong,Peigen Huang,Thomas Yau,Rakesh K Jain,Dan G. Duda
摘要
Immune checkpoint blockade combined with antiangiogenic therapy induces vascular normalization and antitumor immunity and is efficacious in hepatocellular carcinoma (HCC); but whether and how initial immunotherapy affects the efficacy of subsequent antiangiogenic therapy are unknown. We evaluated a cohort of HCC patients (n = 25) who received the pan-vascular endothelial growth factor receptor multikinase inhibitor sorafenib after initial therapy with an antiprogrammed cell death protein (PD)-1 antibody and found superior outcomes in these patients (12% overall response rate to sorafenib and a median overall survival of 12.1 months). To prove this potential benefit, we examined the impact of an anti-PD-1 antibody on response to subsequent sorafenib treatment in orthotopic models of murine HCC. Prior anti-PD-1 antibody treatment amplified HCC response to sorafenib therapy and increased survival (n = 8-9 mice per group, hazard ratio = 0.28, 95% confidence interval = 0.09 to 0.91; 2-sided P = .04). Anti-PD-1 therapy showed angioprotective effects on HCC vessels to subsequent sorafenib treatment, which enhanced the benefit of this therapy sequence in a CD8+ T-cell-dependent manner. This priming approach using immunotherapy provides an immediately translatable strategy for effective HCC treatment while reducing drug exposure.
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