An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model.

An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model.
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在三维共培养模型中量化免疫-肿瘤相互作用的集成框架。

DOI:
10.1038/s42003-021-02296-7
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发表时间:
2021-06-24
影响因子:
5.9
通讯作者:
Flint MS
Flint MS
中科院分区:
生物学2区
文献类型:
--
作者:
Al-Hity G;Yang F;Campillo-Funollet E;Greenstein AE;Hunt H;Mampay M;Intabli H;Falcinelli M;Madzvamuse A;Venkataraman C;Flint MS

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反映免疫系统和肿瘤之间相互作用复杂性的体外研究模型是有限的,而且难以建立。在这里,我们提出了一个平台来研究肿瘤免疫相互作用,使用肿瘤球体和活化的免疫细胞之间的共培养。开发了一种算法,用于分析共培养的共聚焦图像,以定量评估以下内容;免疫细胞浸润,球形圆度和球形生长。为了证明这一概念,我们在66CL4共培养模型上测试了糖皮质激素应激激素皮质醇的作用。结果与66CL4同基因的心理应激小鼠体内模型相当。此外,糖皮质激素受体拮抗剂的施用证明了使用该模型来确定治疗对免疫-肿瘤相互作用的影响。总之,我们提供了一种量化免疫系统与癌症之间相互作用的方法,可以成为免疫治疗设计的筛选工具。al - hity等人提出了一个平台,利用肿瘤球体和活化的免疫细胞之间的共培养来研究肿瘤-免疫相互作用。他们评估了皮质醇应用于培养模型的效果,作为概念验证,这证明了该平台作为免疫治疗设计筛选工具的潜力。
Investigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design. Al-Hity et al present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. They assess the effects of cortisol application to the culture model as proof-of-concept, which demonstrates the potential for this platform as a screening tool for immunotherapy design.
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