Zarobkiewicz Michał K, Lehman Natalia, Kowalska Wioleta, Dąbrowska Izabela, Bojarska-Junak Agnieszka
Department of Clinical Immunology, Medical University of Lublin, Poland.
Department of Interventional Radiology and Neuroradiology, Medical University of Lublin, Poland.
Adv Clin Exp Med. 2025 Jan;34(1):43-52. doi: 10.17219/acem/186335.
Gamma-delta (γδ) T cells comprise an important subset of human T cells, responding to viral and bacterial infections, and are significant for cancer immunosurveillance. Human γδ T cells are divided into 5 major subsets, namely Vδ1-Vδ5, of which the latter 3 have limited available literature. At present, Vδ2 is the most studied subpopulation.
In the current paper, we focused on non-Vδ2 cells in chronic lymphocytic leukemia (CLL). We assessed the expression of co-inhibitory checkpoint receptors (CTLA-4, PD-1 and TIGIT) and co-stimulatory (CD226 and NKp30) molecules separately on Vδ1 and Vδ3-Vδ5 cells.
We assessed γδ T cells for their expression of both cytotoxicity-related (NKp30, CD226) and co-inhibitory (PD-1, TIGIT) molecules with flow cytometry in CLL patients. Moreover, we evaluated the expression of TIGIT and CD226 ligand (PVR , CD155) in neoplastic B cells in CLL patients with quantitative real-time polymerase chain reaction (qPCR).
A significant accumulation of Vδ1 T cells was noted, while no difference was observed in the total percentage of Vδ2 cells. Contrary to our initial hypothesis, the impact of CLL burden on CD226 and TIGIT expression was lower than anticipated. The former tends to be lower in more advanced disease. Finally, a strong upregulation of CD155 (PVR) was noted on CLL-derived B cells when compared to healthy B cells.
Chronic lymphocytic leukemia regulates the expression of the CD155-CD226/TIGIT axis. Contrary to expectations, the ligand is significantly more affected than the receptors. Nevertheless, the relatively high expression of CD155 and TIGIT makes CLL an interesting target for anti-TIGIT immunotherapy.
γδ T细胞是人类T细胞的一个重要亚群，可对病毒和细菌感染作出反应，对癌症免疫监视具有重要意义。人类γδ T细胞分为5个主要亚群，即Vδ1-Vδ5，其中后3个亚群的现有文献有限。目前，Vδ2是研究最多的亚群。
在本文中，我们聚焦于慢性淋巴细胞白血病（CLL）中的非Vδ2细胞。我们分别评估了Vδ1和Vδ3-Vδ5细胞上共抑制检查点受体（CTLA-4、PD-1和TIGIT）和共刺激分子（CD226和NKp30）的表达。
我们通过流式细胞术评估了CLL患者γδ T细胞上细胞毒性相关分子（NKp30、CD226）和共抑制分子（PD-1、TIGIT）的表达。此外，我们用定量实时聚合酶链反应（qPCR）评估了CLL患者肿瘤性B细胞中TIGIT和CD226配体（PVR、CD155）的表达。
我们注意到Vδ1 T细胞显著积聚，而Vδ2细胞的总百分比未观察到差异。与我们最初的假设相反，CLL负荷对CD226和TIGIT表达的影响低于预期。在疾病更晚期，前者往往更低。最后，与健康B细胞相比，我们注意到CLL来源的B细胞上CD155（PVR）有强烈上调。
慢性淋巴细胞白血病调节CD155-CD226/TIGIT轴的表达。与预期相反，配体受影响比受体显著更大。尽管如此，CD155和TIGIT的相对高表达使CLL成为抗TIGIT免疫治疗的一个有吸引力的靶点。
