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索拉非尼治疗晚期肝细胞癌中 m 诱导的铁死亡通过 IFN-γCD8 T 细胞群体的扩张发挥协同作用。

Synergistic activity of m-induced ferroptosis via expansion of IFN-γCD8 T cell population in advanced hepatocellular carcinoma treated with sorafenib.

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

Gut Microbes. 2024 Jan-Dec;16(1):2410474. doi: 10.1080/19490976.2024.2410474. Epub 2024 Oct 1.

DOI:10.1080/19490976.2024.2410474
PMID:39353096
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11445893/
Abstract

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, , , and , are associated with the therapeutic efficacy of Sorafenib, and that (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-γCD8 T cells in the tumor microenvironment. Finally, exopolysaccharides (EPS) from Efm were the primary inducer to prompt IFN-γCD8 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.

摘要

肠道微生物群在肝细胞癌 (HCC) 的发展和治疗中发挥着重要作用。然而，特定的肠道微生物群在索拉非尼靶向治疗晚期 HCC 中的作用机制仍有待阐明。在这里，我们证实了四个细菌属 、 、 、 和 与索拉非尼的治疗效果相关，而 （Efm）在调节索拉非尼活性方面起着关键作用。Efm 的有效定植诱导了肿瘤微环境中 IL-12 和 IFN-γ 的产生以及 IFN-γCD8 T 细胞的比例增加。最后，Efm 的胞外多糖 (EPS) 是促使 IFN-γCD8 T 细胞分泌 IFN-γ的主要诱导剂，与索拉非尼一起引发 HCC 细胞的铁死亡。总之，这些结果表明 Efm 是一种有前途的益生菌，可增强晚期 HCC 患者索拉非尼治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/d4ae7a021b9b/KGMI_A_2410474_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/0db8bc610990/KGMI_A_2410474_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/74b69b798544/KGMI_A_2410474_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/ad6cf025690e/KGMI_A_2410474_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/9902f6af0d6d/KGMI_A_2410474_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/920b7669d301/KGMI_A_2410474_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/5a76d2df3697/KGMI_A_2410474_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/d4ae7a021b9b/KGMI_A_2410474_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/0db8bc610990/KGMI_A_2410474_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/74b69b798544/KGMI_A_2410474_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/ad6cf025690e/KGMI_A_2410474_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/9902f6af0d6d/KGMI_A_2410474_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/920b7669d301/KGMI_A_2410474_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/5a76d2df3697/KGMI_A_2410474_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584d/11445893/d4ae7a021b9b/KGMI_A_2410474_F0007_OC.jpg

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