School of Basic Medical Sciences, Anhui Medical University, No. 81 Meishan Road, Hefei City, Anhui Province, 230032, P.R. China.
Department of Hematology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei City, Anhui Province, 230000, China.
Immunotherapy. 2021 Feb;13(2):113-123. doi: 10.2217/imt-2020-0062. Epub 2020 Oct 20.
To explore the expression of programmed death-1 (PD-1) or programmed death ligand 1 (PD-L1), natural killer T (NKT) and hepatoma cells in coculture system, and the influence of abolishing PD-1 on antitumor efficiency. CRISPR/Cas9 technology, flow cytometry, ELISA, CCK-8 assay and mouse models were performed to investigate the interactions between PD-1/PD-L1 expression on NKT and hepatoma cells, respectively. The NKT and hepatoma cells mutually affected the expression of PD-1/PD-L1. The killing effect was positively correlated with NKT-mediated PD-L1 expression on hepatoma cells. Hepatoma cells in different genetic background responded differently to NKT-induced PD-L1 stimulation, and those cells with lower PD-L1 expression fail to PD-1 blocking intervention. Additionally, the killing effect was more time-efficient with PD-1 knockout than with monoclonal antibody blockade.
探讨共培养体系中程序性死亡受体 1（PD-1）或程序性死亡配体 1（PD-L1）、自然杀伤 T（NKT）细胞和肝癌细胞的表达，以及敲除 PD-1 对肿瘤杀伤效率的影响。采用 CRISPR/Cas9 技术、流式细胞术、ELISA、CCK-8 检测和小鼠模型，分别研究了 NKT 和肝癌细胞上 PD-1/PD-L1 表达之间的相互作用。NKT 和肝癌细胞相互影响 PD-1/PD-L1 的表达。杀伤效应与 NKT 介导的肝癌细胞上 PD-L1 的表达呈正相关。不同遗传背景的肝癌细胞对 NKT 诱导的 PD-L1 刺激的反应不同，表达 PD-L1 较低的细胞无法接受 PD-1 阻断干预。此外，与单克隆抗体阻断相比，PD-1 敲除的杀伤效果更具时效性。
