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:Human decidua basalis mesenchymal stem/stromal cells enhance anticancer properties of human natural killer cells, in vitro.
Human decidua basalis mesenchymal stem/stromal cells enhance anticancer properties of human natural killer cells, in vitro.
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我们得出结论,DBMSCs 对 NK 细胞表现出双重作用,可增强其抗肿瘤治疗潜力。
将DBMSC与从健康人外周血分离的IL-2活化NK细胞或静息未活化NK细胞共培养,并开展多种功能实验,包括NK细胞增殖和细胞溶解活性检测。采用流式细胞术和显微镜观察介导NK细胞对DBMSC细胞溶解作用的受体表达,并进一步研究其作用机制。
DBMSC与NK细胞共培养可抑制静息NK细胞增殖,却提高IL-2活化NK细胞的增殖。相反,较多IL-2活化NK细胞处理可导致DBMSC裂解,而数量较少时则降低DBMSC增殖。NK细胞对DBMSC的细胞溶解作用由多种NK细胞活化受体介导。尽管DBMSC表达HLA I类分子,仍可被NK细胞裂解,说明HLA I类分子未参与该细胞溶解作用。此外,经DBMSC预处理的NK细胞抑制肿瘤细胞增殖的能力增强,严重时可导致肿瘤细胞部分裂解。肿瘤细胞裂解和增殖降低与抗癌作用相关重要分子的表达增加有关。 讨论:我们认为,DBMSC对NK细胞具有双重作用,可增强NK细胞的抗癌治疗潜力。
DBMSCs were cultured with IL-2-activated and resting non-activated NK cells isolated from healthy human peripheral blood and various functional assays were performed including, NK cell proliferation and cytolytic activities. Flow cytometry and microscopic studies were performed to examine the expression of NK cell receptors that mediate these cytolytic activities against DBMSCs. Moreover, the mechanism underlying these effects was also investigated.
Our findings revealed that, co-culture of DBMSCs and NK cells resulted in inhibition of proliferation of resting NK cells, while proliferation of IL-2 activated NK cells was increased. Contrarily, treatment of DBMSC's with comparatively high numbers of IL-2 activated NK cells, resulted in their lysis, whereas treatment with low numbers resulted in reduction in their proliferation. Cytolytic activity of NK cells against DBMSCs was mediated by several activating NK cell receptors. In spite of the expression of HLA class I molecules by DBMSCs, they were still lysed by NK cells, excluding their involvement in cytolytic activity. In addition, preconditioning NK cells by DBMSCs, enhanced their ability to suppress tumor cell proliferation and in severe cases resulted in their partial lysis. Lysis and decrease of tumor cell proliferation is associated with increased expression of important molecules involved in anticancer activities. DISCUSSION: We conclude that DBMSCs exhibit dualfunctions on NK cells that enhance their anticancer therapeutic potential.
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