细胞毒性
肺癌
癌症研究
顺铂
细胞毒性T细胞
免疫系统
CD8型
免疫检查点
下调和上调
吉西他滨
T细胞
药理学
癌症
颗粒酶
化学
化疗
医学
免疫疗法
肿瘤科
免疫学
体外
内科学
生物化学
穿孔素
基因
作者
Min Wang,Hua Guo,Beibei Sun,Xiaohua Jie,Xueyan Shi,Yongqiang Liu,Xu-Liu Shi,Liqin Ding,Peng-Hui Xue,Feng Qiu,Wei Cao,Guizhen Wang,Guang‐Biao Zhou
出处
期刊:Phytomedicine
[Elsevier]
日期:2024-09-01
卷期号:132: 155825-155825
标识
DOI:10.1016/j.phymed.2024.155825
摘要
Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3β-β-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.
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