Introducing innate immunity to 3D tumour models
Cancer drug discovery has been limited by high rates of failure in clinical trials, despite positive laboratory tests suggesting good drug activity. Several types of tumour cell models are used in research labs and by the pharmaceutical industry for discovery and pre-clinical testing of new anti-cancer drugs. Nevertheless, these models still fail to reconstruct the complexity of human solid tumours, as they usually do not account for the role of the immune system in tumour progression and response to therapy.
Researchers from the Animal Cell Technology Unit – Advanced Cell Models Lab have developed a cell model employing tumour and stromal cells, as well as macrophages.
The researchers showed that the model recapitulates features of the tumour niche, including the crosstalk between the different cell players that leads to the immunosuppressive and invasive microenvironment typical of advanced stage carcinomas. In this innovative model, macrophages can infiltrate the tumour mass and acquire a tumour-promoting phenotype. By challenging the model with an immunotherapeutic agent, the authors demonstrated its applicability in testing the efficacy of novel immune-targeting agents, as well as its suitability to study in further detail the molecular mechanisms involved in that response.
These results have been recently published in Biomaterials, one of the top leading journals in biotechnology.
“We have developed a cell model in which the immunosuppressive microenvironment of advanced stage tumours can be recapitulated. Moreover, its design facilitates the adaptation to industrial scales, and therefore can be a useful tool in cancer drug discovery”, state Sofia Rebelo and Catarina Pinto, the co-first authors of the study. “Our model is a new tool to study human macrophage plasticity within the tumoral context and to address tumour-immune interactions in response to external stimuli, such as chemotherapeutic and immunomodulatory drugs”, refers Catarina Brito, head of the Advanced Cell Models Lab (Animal Cell Technology Unit), and leader of this study.
This work was carried out at iBET and ITQB NOVA within the scope of the IMI-funded project PREDECT and of iNOVA4Health, in close collaboration with academic partners (IPOLFG, Lisbon; ICFO, Barcelona) and a pharmaceutical company (Boehringer Ingelheim, a member of the PREDECT consortium). The published paper is freely accessible to all.
Rebelo, S. P., Pinto, C., Martins, T. R., Harrer, N., Estrada, M. F., Loza-Alvarez, P., Cabeçadas, J., Alves, P. M., Gualda, E. J., Sommergruber, W., Brito, C. (2018). 3D-3-culture: A tool to unveil macrophage plasticity in the tumour microenvironment. Biomaterials. https://doi.org/10.1016/j.biomaterials.2018.02.030