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:Non-Classical HLA Class 1b and Hepatocellular Carcinoma.
Non-Classical HLA Class 1b and Hepatocellular Carcinoma.
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目前有多项研究正在进行,旨在更好地理解免疫在肝细胞癌发病机制中的作用,并根据肿瘤病因学识别最可能从全身治疗中获益的个体亚群。人类白细胞抗原在向T细胞呈递抗原中发挥关键作用。这是宿主防御病原体和肿瘤细胞的基础。此外,HLA与固有淋巴细胞受体的特异性相互作用,例如NK 细胞和2型固有淋巴细胞上的受体,已被证明是多种肝脏疾病背景下免疫功能的重要激活因素。更近期的研究强调了非经典HLA-Ib成员以及HLA-F位点邻近转录本FAT10在肝细胞癌中的关键作用。本综述分析了这些分子对肝脏病毒感染和肝细胞癌预后的主要贡献。特别关注了由特定HLA-Ib类分子介导的NK 细胞和Vδ2 T细胞激活与风险评估的关联,以及改善HCC免疫治疗的新策略。
A number of studies are underway to gain a better understanding of the role of immunity in the pathogenesis of hepatocellular carcinoma and to identify subgroups of individuals who may benefit the most from systemic therapy according to the etiology of their tumor. Human leukocyte antigens play a key role in antigen presentation to T cells. This is fundamental to the host's defense against pathogens and tumor cells.
In addition, HLA-specific interactions with innate lymphoid cell receptors, such those present on natural killer cells and innate lymphoid cell type 2, have been shown to be important activators of immune function in the context of several liver diseases. More recent studies have highlighted the key role of members of the non-classical HLA-Ib and the transcript adjacent to the HLA-F locus, FAT10, in hepatocarcinoma.
The present review analyzes the major contribution of these molecules to hepatic viral infection and hepatocellular prognosis. Particular attention has been paid to the association of natural killer and Vδ2 T-cell activation, mediated by specific HLA class Ib molecules, with risk assessment and novel treatment strategies to improve immunotherapy in HCC.
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