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

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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
机构
[1] School of Pharmacy and Biomolecular sciences,Department of Chemical and Process Engineering
[2] University of Brighton,undefined
[3] Centre for Stress and Age-related Diseases,undefined
[4] University of Surrey,undefined
[5] Genome Damage and Stability Centre,undefined
[6] University of Sussex,undefined
[7] Corcept Therapeutics,undefined
[8] School of Mathematical and Physical Sciences,undefined
[9] University of Sussex,undefined
[10] Department of Mathematics,undefined
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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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