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:Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling.
Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling.
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系统性免疫在癌症免疫监视和治疗反应中发挥重要作用,但人们对儿童实体癌患者的免疫状态知之甚少。我们对50名未经治疗的儿童癌症患者进行了系统免疫的高维单细胞分析,并将其与年龄匹配的健康儿童进行比较。癌症患儿外周NK细胞频率较低,这并非由于肿瘤隔离所致,其活化受体表面水平较低,抑制性NKG2A受体水平升高。此外,在体外检测中,儿童癌症患者的自然杀伤(NK)细胞成熟度较低且细胞毒性较弱。将这些NK细胞与interleukin-2共培养可恢复其细胞毒性。总体而言,我们的数据表明,儿童癌症患者中的NK细胞通过多种机制受损,并确定了恢复其功能性的合理策略。
Systemic immunity plays an important role in cancer immune surveillance and response to therapy, but little is known about the immune status of children with solid cancers.
We performed a high-dimensional single-cell analysis of systemic immunity in 50 treatment-naive pediatric cancer patients, comparing them to age-matched healthy children. Children with cancer had a lower frequency of peripheral NK cells, which was not due to tumor sequestration, had lower surface levels of activating receptors and increased levels of the inhibitory NKG2A receptor.
Furthermore, the natural killer (NK) cells of pediatric cancer patients were less mature and less cytotoxic when tested in vitro . Culture of these NK cells with interleukin-2 restored their cytotoxicity. Collectively, our data show that NK cells in pediatric cancer patients are impaired through multiple mechanisms and identify rational strategies to restore their functionality.
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