PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cell on the non-small cell lung cancer (NSCLC) by granzyme B secretion.
PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cell on the non-small cell lung cancer (NSCLC) by granzyme B secretion.
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DOI：
10.1007/s12094-023-03120-w
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发表时间：
2023-08
影响因子：
3.4
通讯作者：
Li, Hai-Jun
中科院分区：
文献类型：
--
作者：
Qiao, Duan-Rui;Cheng, Jun-Ya;Yan, Wei-Qun;Li, Hai-Jun
探讨PD-L1/PD-1阻断在非小细胞肺癌自然杀伤细胞杀伤中的作用。用非放射性细胞毒检测试剂盒检测两种非小细胞肺癌细胞系CALU-1和H460对新鲜分离的健康供体NK细胞的杀伤活性。采用免疫印迹分析、流式细胞仪、酶联免疫吸附试验和抗体阻断实验等方法对其作用机制进行了初步探讨。同时采集非小细胞肺癌患者外周血中的NK细胞进行功能测定。NK细胞对CALU-1和H460细胞的杀伤作用呈剂量依赖关系。在所有比例下，H460细胞对NK细胞介导的裂解的敏感性均低于CALU-1细胞。流式细胞仪和免疫印迹分析显示H460细胞上PD-L1的表达高于CALU-1细胞。抗PD-L1抗体阻断PD-L1/PD-1相互作用后，NK细胞对H460细胞的特异性杀伤作用增强。这一发现也在从NSCLC患者分离的NK细胞中得到证实。本研究发现PD-L1/PD-1阻断可通过分泌颗粒酶B增强自然杀伤细胞对非小细胞肺癌的杀伤作用。本研究将通过测定PD-L1在肿瘤中的表达，为肺癌的精确治疗提供极大的便利。
To explore the role of PD-L1/PD-1 blockage in the cytotoxicity of natural killer cell in NSCLC. Two NSCLC cell lines, Calu-1 and H460, were tested for susceptibility to the cytolytic activity of freshly isolated healthy donor NK cells by a non-radioactive cellular cytotoxicity assay kit. Western blot analysis, FACS, ELISA and antibody blockage experiments were conducted to determine the mechanisms. NK cells isolated from NSCLC patients were also collected for functional assays. Calu-1 and H460 cells were lysed by NK cells in a dose-dependent manner. H460 cells showed less susceptibility to NK cell-mediated lysis than Calu-1 cells at all ratios. The expression of PD-L1 on H460 cells was higher than that on Calu-1 cells, as determined by FACS and western blot analysis. The specific lysis of H460 cells by NK cells was enhanced when the PD-L1/PD-1 interaction was blocked by anti-PD-L1 antibody. This finding was also demonstrated in NK cells isolated from NSCLC patients. The present study revealed that PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cells in NSCLC via granzyme B secretion. This study will greatly facilitate the precise treatment of lung cancer through determination of PD-L1 expression in tumors.
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影响因子：
12.3
作者：
Nagalla S;Chou JW;Willingham MC;Ruiz J;Vaughn JP;Dubey P;Lash TL;Hamilton-Dutoit SJ;Bergh J;Sotiriou C;Black MA;Miller LD
通讯作者：
Miller LD
影响因子：
7.3
作者：
Corgnac S;Boutet M;Kfoury M;Naltet C;Mami-Chouaib F
通讯作者：
Mami-Chouaib F
肝细胞癌中自然杀伤细胞功能障碍和基于 NK 细胞的免疫治疗
影响因子：
8.2
作者：
Sun C;Sun HY;Xiao WH;Zhang C;Tian ZG
通讯作者：
Tian ZG
影响因子：
11.2
作者：
Schmidt, Marcus;Boehm, Daniel;Gehrmann, Mathias
通讯作者：
Gehrmann, Mathias
转移性NSCLC免疫疗法的最新进展。
影响因子：
4.7
作者：
Bansal P;Osman D;Gan GN;Simon GR;Boumber Y
通讯作者：
Boumber Y