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慢性淋巴细胞白血病中γδ T 细胞细胞毒性相关受体的特征分析

英文原题:Characterisation of Cytotoxicity-Related Receptors on γδ T Cells in Chronic Lymphocytic Leukaemia.

PubMed 2025/03/18(内容时间) Cells Q2 · IF 6(JCR 2025)

研究概要

慢性淋巴细胞白血病(CLL)是一种主要影响老年人的血液系统恶性肿瘤,其特征是功能受损的B淋巴细胞增殖,并伴有CD5的异常表达,CD5是一种典型的T细胞标志物。

中文摘要

慢性淋巴细胞白血病(CLL)是一种主要影响老年人的血液系统恶性肿瘤,其特征是功能受损的B淋巴细胞增殖,并伴有CD5的异常表达,CD5是一种典型的T细胞标志物。本研究探讨了CLL患者γδ T细胞上细胞毒性相关受体(CD16、CD56、CD57、CD69)和检查点分子(LAG-3)的表达。共招募了69例未经治疗的CLL患者和14例健康对照。流式细胞术分析显示,与健康对照相比,CLL患者的γδ T细胞上CD56和LAG-3表达较高,CD16表达较低。亚组分析显示,ZAP-70阴性患者CD69表达增加,而CD38阴性患者CD16表达较高。此外,CD16表达与血清LDH水平(一种疾病进展标志物)呈负相关。对CLL数据集中LAG-3配体mRNA的生物信息学分析表明,IGVH未突变患者中HLA-DQA2和HLA-DRB5表达较高。我们的发现突出了CLL中γδ T细胞上关键细胞毒性标志物的表达改变,提示其在疾病进展中的潜在作用以及作为治疗靶点的可能性。特别是,使用抗LAG-3抗体似乎具有前景。

展开英文摘要原文

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy primarily affecting older adults, characterised by the proliferation of functionally impaired B lymphocytes with abnormal expression of CD5, a typical T cell marker. The current study investigates the expression of cytotoxicity-related receptors (CD16, CD56, CD57, CD69) and a checkpoint (LAG-3) on γδ T cells in CLL patients. Sixty-nine treatment-naive CLL patients and fourteen healthy controls were recruited. Flow cytometry analysis revealed that the CLL patients had higher expressions of CD56 and LAG-3 and lower CD16 on their γδ T cells compared to the healthy controls. Subgroup analysis showed that ZAP-70-negative patients exhibited increased CD69, while CD38-negative patients showed higher CD16 expression. Additionally, CD16 expression was inversely correlated with serum LDH levels, a marker of disease progression. Bioinformatic analysis of the LAG-3 ligand mRNA in a CLL dataset indicated higher expression of HLA-DQA2 and HLA-DRB5 in patients with unmutated IGVH . Our findings highlight the altered expression of key cytotoxicity markers on γδ T cells in CLL, suggesting their potential role in disease progression and as a therapeutic target. In particular, the use of anti-LAG-3 antibodies seems promising.

论文信息

作者
Zarobkiewicz M、Lehman N、Morawska-Michalska I、Michalski A、Kowalska W、Szymańska A、Tomczak W、Bojarska-Junak A
单位
Department of Clinical Immunology, Medical University of Lublin, 20-093 Lublin, Poland.Poland
文献类型
非美国政府资助研究
期刊
Cells2025 Mar 18
原文标识
PubMed 40136700 · DOI 10.3390/cells14060451