UNASSIGNED: Each step of NK cytotoxicity against the three MB cell lines was explored using confocal microscopy for conjugation, Elispot for degranulation, flow cytometry, and luminescence assays for target cell necrosis and lysis and mediators released by cytokine array, and then confirmed in a 3D spheroid model. Medulloblastoma-xenografted mice were treated with NK cells. Their persistence was evaluated by flow cytometry, and their efficacy in tumour growth and survival was determined. In addition, their effects on the tumour transcriptome were evaluated.
UNASSIGNED: NK cells showed variable affinities for conjugation with MB target cells depending on their subgroup and cytokine activation. Chemokines secreted during NK and MB cell co-culture are mainly associated with angiogenesis and immune cell recruitment. NK cell cytotoxicity induces MB cell death in both 2D and 3D co-culture models. NK cells initiated an inflammatory response in a human MB murine model by modulating the MB cell transcriptome.
UNASSIGNED: Our study confirmed that NK cells possess both in vitro and in vivo cytotoxic activity against MB cells and are of interest for the development of immunotherapy.
■使用共聚焦显微镜进行接合,探索了针对三种MB细胞系的NK细胞毒性的每个步骤,脱粒的elispot,流式细胞术,以及通过细胞因子阵列释放的靶细胞坏死和裂解以及介质的发光测定,然后在3D球体模型中确认。用NK细胞处理髓母细胞瘤异种移植小鼠。通过流式细胞术评估它们的持久性,并确定了它们在肿瘤生长和存活中的功效。此外,评估了它们对肿瘤转录组的影响。
■NK细胞显示与MB靶细胞结合的不同亲和力,这取决于它们的亚群和细胞因子活化。NK和MB细胞共培养过程中分泌的趋化因子主要与血管生成和免疫细胞募集有关。NK细胞的细胞毒性在2D和3D共培养模型中诱导MB细胞死亡。NK细胞通过调节MB细胞转录组在人MB鼠模型中引发炎症反应。
■我们的研究证实,NK细胞在体外和体内都具有针对MB细胞的细胞毒活性,并对免疫治疗的发展感兴趣。