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:In-depth characterization of NK cell markers from CML patients who discontinued tyrosine kinase inhibitor therapy.
In-depth characterization of NK cell markers from CML patients who discontinued tyrosine kinase inhibitor therapy.
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该 NK 细胞亚群可能在未复发患者中发挥保护作用,因此进一步表征可能对持续深度分子学反应患者有用。
研究通过流式细胞术开展免疫学分析,对患者停药时及其后数月外周血中的特定NK细胞亚群进行检测。
停药时患者NK细胞呈成熟表型,可能与TKI治疗有关。停药3个月后,多种NK细胞受体发生显著变化。CD56dim NK细胞和PD-1阳性NK细胞比例较高的患者,生存机会更好。更值得注意的是,未复发患者还存在一个NK细胞亚群,具有巨细胞病毒感染后扩增相关特征(CD57+NKG2C+表达),且天然细胞毒性受体NKp30和NKp46比例更高;该亚群脱颗粒能力更强,并与更佳生存相关(p<0.0001)。讨论:该NK细胞亚群可能对未复发患者具有保护作用,进一步表征这一亚群或有助于持续获得深度分子应答的患者管理。
In this context, we set up an immunological study by flow cytometry in order to analyze specific NK cell subsets from peripheral blood patient samples both at the time of discontinuation as well as during the subsequent months.
At the time of discontinuation, patients show a mature NK cell phenotype, probably associated to TKI treatment. However, 3 months after discontinuation, significant changes in several NK cell receptors occurred. Patients with a higher proportion of CD56dim NK and PD-1+ NK cells showed better chances of survival. More interestingly, non-relapsing patients also presented a subpopulation of NK cells with features associated with the expansion after cytomegalovirus infection (expression of CD57+NKG2C+), and higher proportion of NKp30 and NKp46 natural cytotoxicity receptors, which resulted in greater degranulation and associated with better survival (p<0.0001). DISCUSSION: This NK cell subset could have a protective role in patients who do not relapse, thus further characterization could be useful for patients in sustained deep molecular response.
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