RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL).
Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL).
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急性淋巴细胞白血病(ALL)是最常见的儿童癌症。多数患者(85%)患 B 细胞 ALL;然而,T 细胞 ALL 通常侵袭性更强。
我们此前发现 2B4(SLAMF4)、CS1(SLAMF7)和 LLT1(CLEC2D)可在与各自配体相互作用后活化或抑制 NK 细胞。
本研究检测了 2B4、CS1、LLT1、NKp30 和 NKp46 的表达。研究者利用圣裘德 PeCan 数据门户的单细胞 RNA 测序数据,分析 B-ALL 和 T-ALL 患者外周血单个核细胞中这些免疫受体的表达谱,发现两类患者 LLT1 表达升高。研究采集 42 例儿童 ALL 患者诊断时及诱导化疗后的全血,以及 20 名健康受试者全血,在 mRNA 和细胞表面蛋白水平检测表达。观察到 T 细胞、单核细胞和 NK 细胞表面 LLT1 表达显著升高。ALL 患者诊断时单核细胞上的 CS1 和 NKp46 表达升高。诱导化疗后,ALL 患者 T 细胞上的 LLT1、2B4、CS1 和 NKp46 表达下降。
此外,mRNA 数据显示 ALL 患者诱导化疗前后受体表达发生变化。结果提示,受体/配体的差异表达可能参与儿童 ALL 中 T 细胞和 NK 细胞介导的免疫监视。
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.
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