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循环 TGF-β1 的增加与转移性黑色素瘤患者 NK 细胞效应功能的损害有关。

Increased circulating TGF-β1 is associated with impairment in NK cell effector functions in metastatic melanoma patients.

机构信息

Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.

Department of Medical Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.

出版信息

Growth Factors. 2022 Nov;40(5-6):231-239. doi: 10.1080/08977194.2022.2124915. Epub 2022 Sep 21.

DOI:10.1080/08977194.2022.2124915
PMID:36129407
Abstract

Transforming growth factor beta (TGF-β) 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-β1 in peripheral blood mononuclear cells by qPCR and serum and supernatant level of free TGF-β1 by ELISA. Melanoma patients had significantly higher serum level of circulatingTGF-β1 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 gene in PBMC. TGF-β1 serum values negatively correlate with NK cell activity analysed by CD107a (degranulation marker), IFN-γ, NKG2D, and NKp46 in patients. Study shows the association of high level of TGF-β1 with NK cell inhibition in patients represents the main mechanism of tumour immune evasion. Targeting TGF-β may become an important cancer treatment for improving antitumor immunity.

摘要

转化生长因子β(TGF-β)在致癌作用中发挥着复杂的作用。我们通过流式细胞术分析了 30 名黑色素瘤患者和 20 名健康对照者(HC)的 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,通过 ELISA 分析了血清和上清液中游离 TGF-β1 的水平。与 HC 相比,黑色素瘤患者的血清循环 TGF-β1 水平显著升高,尤其是那些有中枢神经系统转移(亚类 M1d)和高 LDH 血清值的患者。与 HC 相比,黑色素瘤患者的 PBMC 中基因水平显著升高。TGF-β1 血清值与患者中 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,高水平的 TGF-β1 与患者 NK 细胞抑制有关,这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。

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