封锁
肝细胞癌
PD-L1
癌症研究
基因敲除
免疫疗法
效应器
免疫检查点
细胞生长
mTORC1型
癌症
医学
生物
磷酸化
内科学
细胞培养
免疫学
细胞生物学
受体
生物化学
蛋白激酶B
遗传学
作者
Hui Li,Xiaoqiang Li,Shuang Liu,Lei Guo,Bo Zhang,Jubo Zhang,Qing-Hai Ye
出处
期刊:Hepatology
[Wiley]
日期:2017-11-20
卷期号:66 (6): 1920-1933
被引量:127
摘要
Inhibitors of programmed cell death 1 (PD‐1) administered as single agents have resulted in durable tumor regression in advanced cancer patients. However, only a minority of cancer patients respond to anti‐PD‐1 immunotherapy. Here, we show that PD‐1 expression in hepatocellular carcinoma promotes tumor growth independently of adaptive immunity. Knockdown of PD‐1 suppresses tumor growth, whereas PD‐1 overexpression enhances tumorigenesis in immunodeficient xenografted mice. Mechanistically, PD‐1 binds the downstream mammalian target of rapamycin effectors eukaryotic initiation factor 4E and ribosomal protein S6, thus promoting their phosphorylation. Moreover, combining mammalian target of rapamycin inhibition with anti‐PD‐1 antibody treatment results in more durable and synergistic tumor regression than either single agent alone, each of which presents only modest efficacy. Conclusion: Targeting mammalian target of rapamycin pathways in combination with PD‐1 may result in increased antitumor efficacy in cancer patients. (Hepatology 2017;66:1920–1933)
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