TY - JOUR
T1 - An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model
AU - Al-Hity, Gheed
AU - Yang, FengWei
AU - Campillo-Funollet, Eduard
AU - Greenstein, Andrew E.
AU - Hunt, Hazel
AU - Mampay, Myrthe
AU - Intabli, Haya
AU - Falcinelli, Marta
AU - Madzvamuse, Anotida
AU - Venkataraman, Chandrasekhar
AU - Flint, Melanie S.
PY - 2021/6/24
Y1 - 2021/6/24
N2 - 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.
AB - 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.
UR - https://doi.org/10.1038/s42003-021-02296-7
UR - http://www.scopus.com/inward/record.url?scp=85108793970&partnerID=8YFLogxK
U2 - 10.1038/s42003-021-02296-7
DO - 10.1038/s42003-021-02296-7
M3 - Article
C2 - 34168276
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 781
ER -