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
母胎微嵌合对母体 NK 细胞抗子代白血病原始细胞反应性的影响
英文原题：Influence of Fetomaternal Microchimerism on Maternal NK Cell Reactivity against the Child's Leukemic Blasts.
查看英文原题
Influence of Fetomaternal Microchimerism on Maternal NK Cell Reactivity against the Child's Leukemic Blasts.
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中文摘要
胎儿细胞在母体循环中的持续存在（胎儿微嵌合体，FM）与接受单倍体造血干细胞移植（hHSCT）的白血病患儿生存率提高和复发率降低相关。NK 细胞在母体对胎儿的耐受中发挥重要作用。
本研究前瞻性分析了 70 对母子中 FM 的发生情况、KIR 基因型和 HLA-C 类型。我们发现，FM 的发生及水平受三个母体遗传因素影响：HLA-C1 等位基因的存在、KIR2DL3 的缺失以及 cen-B/B 基序的存在。
此外，母体与子代之间的 HLA-C 匹配有利于 FM 的持续存在。来自 FM + 母体的 NK 细胞针对其子代白血病原始细胞的特异性脱颗粒水平比来自 FM - 母体的 NK 细胞高 40%，提示存在经过教育的母体 NK 细胞。
然而，亲代 NK 细胞对子代白血病原始细胞的细胞毒性独立于 KIR 遗传学（单倍型、B 含量评分、着丝粒和端粒 KIR 基因区域）且独立于 FM，表明额外的免疫效应机制参与了持续性 FM 在 hHSCT 中的有益效应。
展开英文摘要原文
Persistence of fetal cells in the circulation of the mother (fetal microchimerism, FM) is associated with increased survival and reduced relapse of children with leukemia receiving a haploidentical hematopoietic stem cell transplantation (hHSCT). NK cells play an important role in maternal tolerance towards the unborn child. In this study, 70 mother-child pairs were prospectively analyzed for the occurrence of FM, KIR genotype and HLA-C type.
We found that occurrence and level of FM were influenced by three maternal genetic factors: presence of an HLA-C1 allele, absence of KIR2DL3 and presence of a cen-B/B motif.
Furthermore, an HLA-C match between mother and child favored persistence of FM. NK cells from FM + mothers showed a 40% higher specific degranulation against their filial leukemic blasts than NK cells from FM - mothers, suggesting the presence of educated maternal NK cells.
Nevertheless, cytotoxicity of parental NK cells against filial leukemic blasts was independent of KIR genetics (haplotype, B content score, centromeric and telomeric KIR gene regions) and independent of FM, indicating that additional immune effector mechanisms contribute to the beneficial effect of persisting FM in hHSCT.
论文信息
- 作者
- Martin LM、Kruchen A、Fehse B、Müller I
- 单位
- Research Institute Children's Cancer Center Hamburg, 20246 Hamburg, Germany.Germany
- 期刊
- Biomedicines2022 Mar 4
- 原文标识
- PubMed 35327405 · DOI 10.3390/biomedicines10030603
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