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

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Gut Microbes, Vol 16, Iss 1 (2024)
Druh dokumentu: article
ISSN: 19490976
1949-0984
1949-0976
DOI: 10.1080/19490976.2024.2410474
Popis: 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.
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