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

Gheed Abdulmajeed Waleed Al-Hity, Feng Wei Yang, Eduard Campillo-Funollet, Andrew E. Greenstein, Hazel Hunt, Myrthe Mampay, Haya Intabli, Marta Falcinelli, Anotida Madzvamuse, Chandrasekhar Venkataraman, Melanie Flint

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number781
Pages (from-to)1-12
Number of pages12
JournalCommunications Biology
Volume4
Issue number1
DOIs
Publication statusPublished - 24 Jun 2021

Bibliographical note

Funding Information: This work (AM) was supported by an individual grant from the Dr Perry James (Jim) Browne Research Centre on Mathematics and its Applications (University of Sussex). AM’s work was partially funded by grants from the European Union Horizon 2020 research and innovation programme under the Marie Sklodowska–Curie grant agreement (No 642866), the EPSRC (EP/J016780/1, EP/T00410X/1), the Health Foundation (1902431), the NIHR (NIHR133761), and the Leverhulme Trust Research Project Grant (RPG-2014-149). AM is a Royal Society Wolfson Research Merit Award Holder funded generously by the Wolfson Foundation. AM is a Distinguished Visiting Scholar to the Universita degli Studi di Bari Aldo Moro, Bari, Italy and the Department of Mathematics, University of Johannesburg, South Africa. FWY thanks EPSRC(EP/R001588/1) for their funding and support and MF thanks The Boltini tTrust for their funding. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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