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

用于量化三维共培养模型中免疫-肿瘤相互作用的综合框架

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作者:Gheed Al-Hity ,FengWei Yang ,Eduard Campillo-Funollet ,Andrew E Greenstein ,Hazel Hunt ,Myrthe Mampay ,Haya Intabli ,Marta Falcinelli ,Anotida Madzvamuse ,Chandrasekhar Venkataraman ,Melanie S Flint

Abstract

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.

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