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肉瘤患者血液中的免疫生物标志物:一项初步研究。

Immune Biomarkers in Blood from Sarcoma Patients: A Pilot Study.

机构信息

National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Sunway 47500, Malaysia.

出版信息

Curr Oncol. 2022 Aug 5;29(8):5585-5603. doi: 10.3390/curroncol29080441.

Abstract

The main role of the host immune system is to identify and eliminate cancer cells, which is a complex process, but it is not a fail-safe mechanism. Many sarcoma patients succumb to this disease despite treatments rendered. The aim of this pilot study was to compare the levels of CD4+ T-cells, T-regulatory (Treg) cells, and cytokines such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-17A (IL-17A), and transforming growth factor-beta-1 (TGF-β1) in peripheral blood leukocytes of sarcoma patients and healthy controls. For gene expression studies, total ribonucleic acid (RNA) was extracted from peripheral blood leukocytes and genes that were differentially regulated in peripheral blood leukocytes of sarcoma patients compared with healthy controls were determined using a commercial T-helper cell differentiation quantitative polymerase chain reaction (qPCR) array. Flow cytometer analysis was performed on blood samples from 26 sarcoma patients and 10 healthy controls to identify the levels of CD4+ T-cells and T-reg cells. The level of cytokines in plasma and culture supernatant were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. A marked reduction in the percentage of CD4+ T-cells (p = 0.037) and levels of TNF-α (p = 0.004) and IFN-γ (0.010) was observed in sarcoma patients. Gene expression analysis showed five genes (homeobox A10 (HOXA10), GATA binding protein 3 (GATA3), prostaglandin D2 receptor 2 (PTGDR2), thymocyte selection associated high mobility group box (TOX), and C-C motif chemokine receptor 3 (CCR3)) were dysregulated (p < 0.05) in sarcoma patients. This study suggests that T-helper-1 immune responses are reduced in sarcoma patients.

摘要

宿主免疫系统的主要作用是识别和消除癌细胞,这是一个复杂的过程,但它不是万无一失的机制。尽管进行了治疗,许多肉瘤患者还是死于这种疾病。本初步研究的目的是比较肉瘤患者和健康对照者外周血白细胞中 CD4+T 细胞、调节性 T 细胞(Treg)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、白细胞介素-17A(IL-17A)和转化生长因子-β-1(TGF-β1)等细胞因子的水平。为了进行基因表达研究,从外周血白细胞中提取总核糖核酸(RNA),并使用商业 T 辅助细胞分化定量聚合酶链反应(qPCR)阵列确定与健康对照者相比,肉瘤患者外周血白细胞中差异调节的基因。对 26 名肉瘤患者和 10 名健康对照者的血液样本进行流式细胞仪分析,以确定 CD4+T 细胞和 Treg 细胞的水平。使用商业酶联免疫吸附试验(ELISA)试剂盒定量测定血浆和培养上清液中细胞因子的水平。与健康对照组相比,肉瘤患者 CD4+T 细胞的百分比(p=0.037)和 TNF-α(p=0.004)及 IFN-γ(0.010)水平显著降低。基因表达分析显示,在肉瘤患者中,有 5 个基因(同源盒 A10(HOXA10)、GATA 结合蛋白 3(GATA3)、前列腺素 D2 受体 2(PTGDR2)、胸腺细胞选择相关高迁移率族框(TOX)和 C-C 基序趋化因子受体 3(CCR3))失调(p<0.05)。本研究表明,辅助性 T 细胞 1 型免疫应答在肉瘤患者中降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/9406743/e660c53a6852/curroncol-29-00441-g001.jpg

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