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:Cord blood stem cell-generated KIR(+)NK cells effectively target leukemia cell lines.
Cord blood stem cell-generated KIR(+)NK cells effectively target leukemia cell lines.
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急性淋巴细胞白血病(ALL)和急性髓系白血病(AML)是已知具有侵袭性且高度致命的血液系统恶性肿瘤。由于当前治疗方法不足且具有多种副作用,研究人员正在寻找新的更有效的治疗方法。有趣的是,持续努力寻找优化NK细胞抗白血病潜力的最佳方法,为癌症的成功治疗带来了希望。成熟KIR+NK细胞清除HLA I类缺陷细胞的能力已被用于癌症免疫治疗。在此,我们利用IL-2和IL-15细胞因子从脐带血干细胞中生成了KIR+NK细胞。我们的发现强调了KIR表达在NK细胞细胞毒功能中的重要性。综上所述,本研究提出了一种有效的体外方法,利用细胞因子在无饲养层细胞的条件下扩增和分化KIR+NK细胞。此外,所提出的培养条件可用于从有限数量的CD34+脐带血细胞中生成成熟且纯净的NK细胞,并可能作为一种新方法用于改善当前癌症治疗的状态。
Acute lymphoid (ALL) and myeloid leukemia (AML) are known to be invasive and highly lethal hematological malignancies. Because current treatments are insufficient and have a variety of side effects, researchers are looking for new and more effective therapeutic methods. Interestingly, ongoing efforts to find the best approach to optimize NK cell anti-leukemia potential shed light on the successful treatment of cancer. Mature KIR + NK cells ability to remove HLA Class-I deficient cells has been exploited in cancer immunotherapy.
Here, we generated KIR + NK cells from cord blood stem cells using IL-2 and IL-15 cytokines.
Our finding underlined the importance of KIR expression in the cytotoxic function of NK cells. Taken together, this study presented an effective in vitro method for the expansion and differentiation of KIR + NK cells using cytokines without any feeder cells.
Furthermore, the presented culture condition could be useful for the generation of mature and pure NK cells from limited numbers of CD34 + cord blood cells and might be used as a novel method to improve the current state of cancer therapy.
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