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:Immune landscape of hepatocellular carcinoma: From dysregulation of the immune responses to the potential immunotherapies.
Immune landscape of hepatocellular carcinoma: From dysregulation of the immune responses to the potential immunotherapies.
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肝细胞癌(HCC)由于诊断晚和发病率高,构成了巨大的全球健康负担。肝脏特定的解剖和生理特征使其暴露于多种抗原,需要精确的免疫调节。据我们所知,这是首次全面概述免疫系统与肠道微生物群在HCC发展中的相互作用以及相关治疗方法。肝脏微环境中免疫区室的失调驱动HCC发病机制,其特征是调节性细胞如调节性T细胞(Tregs)、髓源性抑制细胞和M2巨噬细胞以及抑制性分子升高,同时效应细胞如T细胞、NK 细胞和M1巨噬细胞数量减少。肠道微生物群失调也通过破坏肠道屏障完整性和触发过度激活的免疫反应促进HCC。免疫治疗方法,特别是免疫检查点抑制剂,在HCC管理中显示出前景,但过继细胞疗法和癌症疫苗研究仍处于早期阶段,结果相对不太理想。进一步了解免疫失调、肠道微生物群参与和治疗组合策略对于推进HCC精准免疫治疗至关重要。
Hepatocellular carcinoma (HCC) presents a considerable global health burden due to its late diagnosis and high morbidity. The liver's specific anatomical and physiological features expose it to various antigens, requiring precise immune regulation. To the best of our knowledge, this is the first time that a comprehensive overview of the interactions between the immune system and gut microbiota in the development of HCC, as well as the relevant therapeutic approaches are discussed.
Dysregulation of immune compartments within the liver microenvironment drives HCC pathogenesis, characterized by elevated regulatory cells such as regulatory T cells (Tregs), myeloid-derived suppressor cells, and M2 macrophages as well as suppressive molecules, alongside reduced number of effector cells like T cells, natural killer cells, and M1 macrophages.
Dysbiosis of gut microbiota also contributes to HCC by disrupting intestinal barrier integrity and triggering overactivated immune responses. Immunotherapy approaches, particularly immune checkpoint inhibitors, have exhibited promise in HCC management, yet adoptive cell therapy and cancer vaccination research are in the early steps with relatively less favorable outcomes.
Further understanding of immune dysregulation, gut microbiota involvement, and therapeutic combination strategies are essential for advancing precision immunotherapy in HCC.
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