Soluble programmed death ligand-1-induced immunosuppressive effects on chimeric antigen receptor-natural killer cells targeting Glypican-3 in hepatocellular carcinoma.
Soluble programmed death ligand-1-induced immunosuppressive effects on chimeric antigen receptor-natural killer cells targeting Glypican-3 in hepatocellular carcinoma.
复制标题
可溶性程序性死亡配体-1诱导的靶向Glypican-3的嵌合抗原受体-自然杀伤细胞在肝癌中的免疫抑制作用
作者：
Although the pre-clinical study of chimeric antigen receptor (CAR)-natural killer (NK) cell was effective against various tumours, immunosuppression mediated by tumour microenvironment hampers their application and several efforts have been explored to improve their effect in combating solid tumours. Glypican 3 (GPC3) is a promising target for hepatocellular carcinoma (HCC), and CAR-T cells targeting GPC3 have been tested in clinical trials. Based on an affinity-enhanced antibody (hYP7) targeting GPC3, we constructed GPC3-CAR-NK cells to explore their potential function in the treatment of HCC. We found that patients with HCC secreted high levels of soluble programmed death-ligand 1 (sPD-L1), which inhibits the function of CAR-NK cells targeting GPC3. In addition, we combined high-affinity sPD-L1 variant (L3C7c-Fc) with GPC3-CAR-NK cells to solve the problem of GPC3-CAR-NK inhibition. Our studies demonstrated that L3C7c-Fc could enhance the therapeutic effect of CAR-NK cells by reversing the suppression of sPD-L1, which provides the experimental evidence for the subsequent development of HCC immunotherapy strategies.
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影响因子：
24.5
作者：
Chew V;Chen J;Lee D;Loh E;Lee J;Lim KH;Weber A;Slankamenac K;Poon RT;Yang H;Ooi LL;Toh HC;Heikenwalder M;Ng IO;Nardin A;Abastado JP
通讯作者：
Abastado JP
开发夹心 ELISA，用于评估不同年龄的人血清以及 PD-L1 细胞系上清液中的可溶性 PD-L1 (CD274)。
影响因子：
3.8
作者：
Chen, Yongjing;Wang, Qin;Zhang, Xueguang
通讯作者：
Zhang, Xueguang
PD-1检查点途径的分子和生化方面。
DOI：
10.1056/nejmra1514296
发表时间：
2016-11-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Boussiotis VA
通讯作者：
Boussiotis VA
影响因子：
11.4
作者：
Liu E;Tong Y;Dotti G;Shaim H;Savoldo B;Mukherjee M;Orange J;Wan X;Lu X;Reynolds A;Gagea M;Banerjee P;Cai R;Bdaiwi MH;Basar R;Muftuoglu M;Li L;Marin D;Wierda W;Keating M;Champlin R;Shpall E;Rezvani K
通讯作者：
Rezvani K
NK 细胞上程序性细胞死亡蛋白 1 的表达增加会抑制 NK 细胞介导的抗肿瘤功能，并表明消化道癌症的预后不良
影响因子：
8
作者：
Liu Y;Cheng Y;Xu Y;Wang Z;Du X;Li C;Peng J;Gao L;Liang X;Ma C
通讯作者：
Ma C