Zarobkiewicz Michał, Lehman Natalia, Morawska-Michalska Izabela, Michalski Adam, Kowalska Wioleta, Szymańska Agata, Tomczak Waldemar, Bojarska-Junak Agnieszka
Department of Clinical Immunology, Medical University of Lublin, 20-093 Lublin, Poland.
Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-080 Lublin, Poland.
Cells. 2025 Mar 18;14(6):451. doi: 10.3390/cells14060451.
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 and in patients with unmutated . 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.
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，并异常表达典型的T细胞标志物CD5。本研究调查了CLL患者γδT细胞上细胞毒性相关受体（CD16、CD56、CD57、CD69）和一个检查点（LAG-3）的表达情况。招募了69例未经治疗的CLL患者和14名健康对照者。流式细胞术分析显示，与健康对照者相比，CLL患者γδT细胞上CD56和LAG-3的表达较高，而CD16的表达较低。亚组分析表明，ZAP-70阴性患者的CD69表达增加，而CD38阴性患者的CD16表达较高。此外，CD16表达与疾病进展标志物血清乳酸脱氢酶水平呈负相关。对一个CLL数据集的LAG-3配体mRNA进行生物信息学分析表明，未突变患者中 和 的表达较高。我们的研究结果突出了CLL患者γδT细胞上关键细胞毒性标志物表达的改变，表明它们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抗体似乎很有前景。
