RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.
Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.
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细菌代谢物在肝细胞癌(HCC)中发挥双重作用,因其结构多样性而表现出促肿瘤和抑肿瘤两种活性。本综述综合了关于关键微生物代谢物——如胆汁酸、短链脂肪酸和多胺——如何通过免疫代谢重编程、表观遗传修饰以及信号通路(如 FXR、TLR 和 mTOR)调控等机制重塑肿瘤免疫微环境的最新进展。我们重点阐述了这些代谢物在调节 T 细胞、NK 细胞和肿瘤相关巨噬细胞功能中的作用,并讨论了靶向这些代谢物的新兴策略——包括益生菌干预、粪菌移植和基于代谢物的佐剂——以增强免疫治疗疗效并克服耐药。通过将机制见解与转化潜力相结合,本工作勾勒出代谢物-免疫代谢-肝癌发生框架,并提出用于 HCC 治疗的新型联合方案。
Bacterial metabolites play a dual role in hepatocellular carcinoma (HCC), exhibiting both tumor-promoting and tumor-suppressing activities dictated by their structural diversity. This review synthesizes recent advances in understanding how key microbial metabolites-such as bile acids, short-chain fatty acids, and polyamines-remodel the tumor immune microenvironment through mechanisms including immunometabolic reprogramming, epigenetic modification, and regulation of signaling pathways (e. g. , FXR, TLR, and mTOR).
We highlight their roles in modulating the function of T cells, NK cells, and tumor-associated macrophages and discuss emerging strategies that target these metabolites-including probiotic interventions, fecal microbiota transplantation, and metabolite-based adjuvants-to enhance immunotherapy efficacy and overcome resistance. By integrating mechanistic insight into translational potential, this work outlines a metabolite-immunometabolism-hepatocarcinogenesis framework and proposes novel combinatorial approaches for HCC treatment.
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