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:Increased circulating TGF-β1 is associated with impairment in NK cell effector functions in metastatic melanoma patients.
Increased circulating TGF-β1 is associated with impairment in NK cell effector functions in metastatic melanoma patients.
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转化生长因子β(TGF-β)在癌变过程中发挥复杂作用。在30例黑色素瘤患者和20例健康对照(HC)中,我们通过流式细胞术分析了NK细胞的功能和表型特征,通过qPCR分析了外周血单个核细胞中TGF-β1的基因表达,并通过ELISA分析了血清和上清液中游离TGF-β1的水平。黑色素瘤患者的循环TGF-β1血清水平显著高于HC,尤其是那些有中枢神经系统转移(M1d亚类)和血清LDH值高的患者。与HC相比,黑色素瘤患者PBMC中TGF-β1基因水平显著更高。患者中TGF-β1血清值与通过CD107a(脱颗粒标志物)、IFN-γ、NKG2D和NKp46分析的NK细胞活性呈负相关。研究表明,患者中高水平TGF-β1与NK细胞抑制的关联代表了肿瘤免疫逃逸的主要机制。靶向TGF-β可能成为改善抗肿瘤免疫的重要癌症治疗方法。
Transforming growth factor beta (TGF- ) plays a complex role in carcinogenesis. In 30 melanoma patients and 20 healthy controls (HC) we analysed functional and phenotypic characteristics of NK cells by Flow cytometry, gene expression of TGF- 1 in peripheral blood mononuclear cells by qPCR and serum and supernatant level of free TGF- 1 by ELISA. Melanoma patients had significantly higher serum level of circulatingTGF- 1 compared to HC, especially those with metastasis into the central nervous system (subclass M1d) and high LDH serum values.
Melanoma patients compared to HC had significantly higher level of TGF- 1 gene in PBMC. TGF- 1 serum values negatively correlate with NK cell activity analysed by CD107a (degranulation marker), IFN- , NKG2D, and NKp46 in patients. Study shows the association of high level of TGF- 1 with NK cell inhibition in patients represents the main mechanism of tumour immune evasion. Targeting TGF- may become an important cancer treatment for improving antitumor immunity.
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