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:USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.
USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.
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本研究考察去泛素化酶 USP47 在肿瘤微环境中的作用及其对抗肿瘤免疫反应的影响。对 TCGA 数据库的分析发现,USP47 在多种肿瘤组织和正常组织中呈现不同表达模式。与正常组织相比,前列腺腺癌中 USP47 显著下调。相关性分析显示,USP47 表达水平与浸润的 CD8+ T 细胞、中性粒细胞和巨噬细胞呈正相关,与 NKT 细胞呈负相关。此外,在 Usp47 基因敲除小鼠中,肿瘤生长速度减慢,肿瘤负荷降低。缺失 USP47 会增加包括中性粒细胞、巨噬细胞、NK 细胞、NKT 细胞和 T 细胞在内的免疫细胞浸润。此外,USP47 缺失增强了细胞毒性 T 淋巴细胞(CTL)的活化,并改变肿瘤微环境中的 T 细胞亚群。这些发现提示 USP47 在调节肿瘤微环境并促进抗肿瘤免疫反应方面发挥关键作用,凸显其作为前列腺癌治疗靶点的潜力。
This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues.
Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8 + T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells.
Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells.
Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment.
These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.
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