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
自体造血干细胞移植后 CD9⁺ 蜕膜样 NK 细胞亚群的体内扩增
英文原题：In vivo expansion of a CD9(+) decidual-like NK cell subset following autologous hematopoietic stem cell transplantation.
查看英文原题
In vivo expansion of a CD9(+) decidual-like NK cell subset following autologous hematopoietic stem cell transplantation.
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中文摘要
自体造血干细胞移植（autoHSCT）是治疗血液系统疾病和儿童实体瘤的一种选择。autoHSCT后，自然杀伤（NK）细胞是最先恢复至正常水平的淋巴细胞亚群。为揭示autoHSCT后NK细胞重建期间的全局变化，我们对autoHSCT前后NK细胞进行RNA测序。结果显示，autoHSCT后NK细胞基因表达谱立即发生显著变化。细胞周期、DNA复制和甲羟戊酸途径等多项生物学过程富集。值得注意的是，autoHSCT后NK细胞获得蜕膜样基因表达谱，包括CD9表达。通过多参数流式细胞术，我们证实autoHSCT后立即出现CD9表达NK细胞扩增；与CD9− NK细胞相比，该亚群颗粒酶B和穿孔素表达水平更高。这些结果有助于理解autoHSCT后NK细胞重建期间的病理生理过程。
展开英文摘要原文
Autologous hematopoietic stem cell transplantation (autoHSCT) is a treatment option for hematological disorders and pediatric solid tumors. After an autoHSCT, natural killer (NK) cells are the first lymphocyte subset returning to normal levels. To uncover global changes during NK cell reconstitution after autoHSCT, we performed RNA-sequencing on NK cells before and after autoHSCT. Results showed profound changes in the gene expression profile of NK cells immediately after autoHSCT.
Several biological processes including cell cycle, DNA replication and the mevalonate pathway were enriched. Significantly, we observed that following autoHSCT, NK cells acquired a decidual-like gene expression profile, including the expression of CD9.
By using multiparametric flow cytometry, we confirmed the expansion of NK cells expressing CD9 immediately after autoHSCT, which exhibited higher granzyme B and perforin expression levels than CD9 - NK cells. These results provide insights into the physiopathology of NK cells during their reconstitution after autoHSCT.
论文信息
- 作者
- Orrantia A、Vázquez-De Luis E、Astarloa-Pando G、Terrén I、Amarilla-Irusta A、Polanco-Alonso D、González C、Uranga A
- 单位
- Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.Spain
- 期刊
- iScience2022 Oct 21
- 原文标识
- PubMed 36262311 · DOI 10.1016/j.isci.2022.105235
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