Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Int J Mol Sci. 2023 Feb 15;24(4):3860. doi: 10.3390/ijms24043860.
Acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL; however, T-cell ALL tends to be more aggressive. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 (CLEC2D) that can activate or inhibit NK cells upon the interaction with their ligands. In this study, the expression of 2B4, CS1, LLT1, NKp30 and NKp46 was determined. The expression profiles of these immune receptors were analyzed in the peripheral blood mononuclear cells of B-ALL and T-ALL subjects by single-cell RNA sequencing data obtained from the St. Jude PeCan data portal that showed increased expression of LLT1 in B-ALL and T-ALL subjects. Whole blood was collected from 42 pediatric ALL subjects at diagnosis and post-induction chemotherapy and 20 healthy subjects, and expression was determined at the mRNA and cell surface protein level. A significant increase in cell surface LLT1 expression in T cells, monocytes and NK cells was observed. Increased expression of CS1 and NKp46 was observed on monocytes of ALL subjects at diagnosis. A decrease of LLT1, 2B4, CS1 and NKp46 on T cells of ALL subjects was also observed post-induction chemotherapy. Furthermore, mRNA data showed altered expression of receptors in ALL subjects pre- and post-induction chemotherapy treatment. The results indicate that the differential expression of the receptors/ligand may play a role in the T-cell- and NK-cell-mediated immune surveillance of pediatric ALL.
急性淋巴细胞白血病 (ALL) 是最常见的儿科癌症。大多数患者（85%）患有 B 细胞 ALL；然而，T 细胞 ALL 往往更具侵袭性。我们之前已经鉴定出 2B4（SLAMF4）、CS1（SLAMF7）和 LLT1（CLEC2D），它们在与配体相互作用时可以激活或抑制 NK 细胞。在这项研究中，测定了 2B4、CS1、LLT1、NKp30 和 NKp46 的表达。通过从圣裘德 PeCan 数据门户获得的单细胞 RNA 测序数据，分析了这些免疫受体在 B-ALL 和 T-ALL 受试者外周血单个核细胞中的表达谱，该数据显示 LLT1 在 B-ALL 和 T-ALL 受试者中的表达增加。从 42 名儿科 ALL 受试者在诊断和诱导化疗后以及 20 名健康受试者采集全血，并在 mRNA 和细胞表面蛋白水平上测定表达。观察到 T 细胞、单核细胞和 NK 细胞表面 LLT1 表达显著增加。在 ALL 受试者的单核细胞中观察到 CS1 和 NKp46 的表达增加。在诱导化疗后，也观察到 ALL 受试者 T 细胞上的 LLT1、2B4、CS1 和 NKp46 减少。此外，mRNA 数据显示 ALL 受试者在诱导化疗前后受体表达发生改变。结果表明，受体/配体的差异表达可能在儿科 ALL 的 T 细胞和 NK 细胞介导的免疫监视中发挥作用。
