研究动态
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在索拉非尼治疗的晚期肝细胞癌中,屎肠球菌通过扩增 IFN-γ CD8 T 细胞群诱导铁死亡的协同活性。

Synergistic activity of Enterococcus Faecium-induced ferroptosis via expansion of IFN-γ+CD8+ T cell population in advanced hepatocellular carcinoma treated with sorafenib.

发表日期:2024
作者: Haitao Yu, Ganglian Lin, Junyan Jiang, Jiangqiao Yao, Zhenyan Pan, Haonan Xie, Zhiyuan Bo, Qikuan He, Jinhuan Yang, Ziyan Chen, Jiacheng Li, Yi Wang, Zhengping Yu, Yehuda G Assaraf, Gang Chen
来源: Gut Microbes

摘要:

肠道微生物群在肝细胞癌(HCC)的发生和治疗中发挥着重要作用。然而,特定肠道微生物群在晚期 HCC 靶向索拉非尼治疗中的意义以及微生物群的作用模式仍有待阐明。在这里,我们证实了四种细菌属,毛梭菌属、毛螺菌属、肠杆菌属和肠球菌属与索拉非尼的治疗效果相关,并且屎肠杆菌(Efm)在调节索拉非尼活性中起着至关重要的作用。 Emf 的有效定植诱导了 IL-12 和 IFN-γ 的产生,并增加了肿瘤微环境中 IFN-γ CD8 T 细胞的比例。最后,Efm 的胞外多糖 (EPS) 是促使 IFN-γ CD8 T 细胞分泌 IFN-γ 的主要诱导剂,与索拉非尼一起引发 HCC 细胞铁死亡。总的来说,这些结果表明 Efm 是一种有前途的益生菌,可增强索拉非尼治疗晚期 HCC 的疗效。
The gut microbiota plays an important role in the development and treatment of hepatocellular carcinoma (HCC). However, the implication of specific gut microbiota in targeted sorafenib therapy for advanced HCC and the microbiota mode of action, remain to be elucidated. Here, we confirmed that four bacterial genera, Lachnoclostridium, Lachnospira, Enterobacter and Enterococcus, are associated with the therapeutic efficacy of Sorafenib, and that Enterobacter faecium (Efm) plays a crucial role in modulating the sorafenib activity. The effective colonization by Emf induced the IL-12 and IFN-γ production and an increased proportion of IFN-γ+CD8+ T cells in the tumor microenvironment. Finally, exopolysaccharides (EPS) from Efm were the primary inducer to prompt IFN-γ+CD8+ T cells to secrete IFN-γ, which together with sorafenib instigated ferroptosis in HCC cells. Collectively, these results indicate that Efm is a promising probiotics that enhances the efficacy of sorafenib treatment in advanced HCC.