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:Optimized flow cytometry panel for the detection and analysis of human tumor-induced memory-like NK cells.
Optimized flow cytometry panel for the detection and analysis of human tumor-induced memory-like NK cells.
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近期研究表明,在特定条件下,如病毒感染或暴露于促炎细胞因子时,NK 细胞可能获得适应性免疫细胞的特征。在此背景下,已有多种形式的适应性 NK 细胞被描述,即“肝脏驻留”记忆样 NK 细胞、巨细胞病毒(CMV)诱导的记忆 NK 细胞以及白细胞介素(IL)12/15/18 细胞因子诱导的记忆样(CIML)-NK 细胞。
我们近期提供证据表明,在与经照射的白血病标本共培养 7 天后,NK 细胞可表现出记忆样表型,并具有显著抗白血病功能。在此,我们提出一组抗体组合,可用于识别这些所谓肿瘤诱导记忆样(TIML)-NK 细胞在记忆细胞转化过程中激活状态和成熟度的细微变化,也可将这些细胞与其他形式的记忆 NK 细胞进行比较。鉴于目前正在开展大量工作以评估不同形式 NK 细胞过继性细胞转移的临床获益,我们在此详细描述我们的组合设计过程,以便未来研究人员能够在临床试验方案中优化各种形式记忆 NK 细胞的流式细胞术分析。
Recent studies indicate that under certain conditions such as viral infection or exposure to pro-inflammatory cytokines, NK cells may acquire features of adaptive immune cells. In this context, various forms of adaptive NK cells have been described, i. e. "liver-resident" memory-like NK cells, cytomegalovirus (CMV)-induced memory NK cells and interleukin (IL)12/15/18 cytokine-induced memory-like (CIML)-NK cells.
We recently provided evidence that upon a 7-day co-culture with irradiated leukemia specimens NK cells can exhibit a memory-like phenotype with substantial anti-leukemic functionality.
Here, we propose an antibody panel that allows the identification of subtle changes in the activation status and maturation during memory cell conversion of these so-called tumor-induced memory-like (TIML)-NK cells but also the comparison of those with other forms of memory NK cells.
As tremendous efforts are currently undertaken to evaluate the clinical benefit of adoptive cell transfer of various forms of NK cells, we here delineate the process of our panel design in detail to provide future researchers with the means to optimize the flow cytometric analysis of various forms of memory NK cells within their clinical trial protocols.
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