当前位置: X-MOL 学术Clin. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Cisplatin inhibits the progression of bladder cancer by selectively depleting G-MDSCs: A novel chemoimmunomodulating strategy
Clinical Immunology ( IF 8.6 ) Pub Date : 2018-02-02 , DOI: 10.1016/j.clim.2018.01.012
Ke Wu , Ming-Yue Tan , Jun-Tao Jiang , Xing-Yu Mu , Jie-Ren Wang , Wen-Jie Zhou , Xiang Wang , Ming-qing Li , Yin-Yan He , Zhi-Hong Liu

Bladder cancer (BC) is a disease arising from the malignant cells of the urinary bladder. Myeloid-derived suppressor cells (MDSCs) expand broadly and have strong immunosuppressive activities in the cancer microenvironment. Determining how to inhibit the negative effects of MDSCs requires immediate attention. In this study, we found that granulocytic-MDSCs (G-MDSCs), which constitute one of the two types of MDSCs, were significantly increased in BC tissues compared with those in the adjacent bladder tissues. There was a robust negative correlation between the G-MDSCs and the CD8+ T cells in the BC tissues. In this study, we attempted to identify pharmacological approaches to eliminate MDSCs and restore T cell anti-tumor activities. It is necessary to explore a method to eliminate the detrimental effects of MDSCs. Cisplatin, a chemotherapy medication used to treat BC, not only rapidly kills proliferating cancer cells but also affects the tumor immune microenvironment. However, the mechanism underlying this phenomenon is largely unknown. In this study, we found that Cisplatin directly inhibited the proliferation and induced the apoptosis of T24 cells (a BC cell line), as well as decreased the percentage of the G-MDSCs in the population of peripheral blood mononuclear cells (PBMCs), which restored the expansion of the CD8+ T cells. In the C3H/He mouse BC model, Cisplatin treatment inhibited the progression of BC and effectively decreased the proportion of G-MDSCs. These results suggest that Cisplatin treatment enhances the anti-tumor function of CD8+ T cells by decreasing G-MDSCs. This finding provides a new perspective for Cisplatin treatment to prevent the progression of BC, particularly in patients with abnormally high levels of G-MDSCs.



中文翻译:

顺铂通过选择性消耗G-MDSCs抑制膀胱癌的发展:一种新型的化学免疫调节策略

膀胱癌(BC)是由膀胱恶性细胞引起的疾病。髓样来源的抑制细胞(MDSCs)在癌症微环境中广泛扩展并具有强大的免疫抑制活性。确定如何抑制MDSC的负面影响需要立即关注。在这项研究中,我们发现,与相邻膀胱组织相比,构成两种MDSC之一的粒细胞MDSC(G-MDSC)在BC组织中显着增加。G-MDSC与CD8 +之间存在强烈的负相关关系BC组织中的T细胞。在这项研究中,我们试图确定消除MDSCs和恢复T细胞抗肿瘤活性的药理学方法。有必要探索一种消除MDSC有害影响的方法。顺铂是一种用于治疗BC的化学疗法药物,它不仅可以迅速杀死正在增殖的癌细胞,还可以影响肿瘤的免疫微环境。但是,这种现象的潜在机制在很大程度上尚不清楚。在这项研究中,我们发现顺铂直接抑制T24细胞(一种BC细胞系)的增殖并诱导其凋亡,并降低了外周血单个核细胞(PBMC)群体中G-MDSC的百分比,恢复了CD8 +的扩展T细胞。在C3H / He小鼠BC模型中,顺铂治疗可抑制BC的进展并有效降低G-MDSC的比例。这些结果表明,顺铂治疗可通过减少G-MDSCs增强CD8 + T细胞的抗肿瘤功能。这一发现为顺铂治疗预防BC的进展提供了新的视角,特别是对于G-MDSCs异常高的患者。

更新日期:2018-02-02
down
wechat
bug