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
USP15 高表达影响肝细胞癌的肿瘤进展和免疫浸润
英文原题：High expression of USP15 affects tumor progression and immune infiltration in hepatocellular carcinoma.
查看英文原题
High expression of USP15 affects tumor progression and immune infiltration in hepatocellular carcinoma.
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研究概要
USP15 通过抑制 T 细胞和 NK 细胞浸润、促进程序性死亡配体 1（PD-L1）介导的免疫逃逸以及增强巨噬细胞募集，促进 HCC 中免疫抑制性肿瘤微环境的建立。这些发现表明，USP15 可能作为 HCC 的潜在治疗靶点。
研究思路结论见上方概要
背景
泛素特异性蛋白酶15（USP15）与肝细胞癌（HCC）的发生和进展密切相关。然而，其塑造HCC免疫景观的作用仍不清楚。
方法
采用多重免疫组化（mIHC）评估HCC组织中USP15及特定免疫细胞亚群的表达水平、比例和空间分布。
结果
在HCC组织的肿瘤实质中，免疫细胞尤其是自然杀伤（NK）细胞的浸润显著减少（p<0.05）。进一步分析显示，USP15表达水平与临床分期及其他临床病理参数显著相关（p<0.05）。特别是，NK细胞浸润与N分期、M分期及整体肿瘤-淋巴结-转移（TNM）分期显著相关（p<0.05）。
展开英文摘要原文
MATERIALS AND METHODS
The expression levels, proportions, and spatial distributions of USP15 and specific immune cell subsets in HCC tissues were evaluated using multiplex immunohistochemistry (mIHC).
RESULTS
In the tumor parenchyma of HCC tissues, the infiltration of immune cells, particularly natural killer (NK) cells, was significantly reduced (p<0.05). Further analyses revealed that USP15 expression levels were significantly associated with clinical stage and other clinicopathological parameters (p<0.05). In particular, NK cell infiltration was significantly correlated with N stage, M stage, and overall tumor-node-metastasis (TNM) stage (p<0.05).
CONCLUSION
USP15 contributes to the establishment of an immunosuppressive tumor microenvironment in HCC by inhibiting T cell and NK cell infiltration, facilitating programmed death-ligand 1 (PD-L1)-mediated immune evasion, and enhancing macrophage recruitment. These findings indicate that USP15 may serve as a potential therapeutic target for HCC.
论文信息
- 作者
- Wu SP、Zhang XY、Chen HD、Jin FZ、Jiang N、Zhang JX、Liang ZL
- 第一作者单位
- Medical College of Yanbian University, Jilin, China.China
- 通讯作者单位
- Department of Anesthesia, Hospital of Yanbian University, Jilin, China.China
- 期刊
- Hepatology forum2026
- 原文标识
- PubMed 42564509 · DOI 10.14744/hf.2026.39981
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