Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing

Immunotherapies are beneficial for a considerable proportion of cancer patients, but ineffective in others. In vitro modelling of the complex interactions between cancer cells and their microenvironment could provide a path to understanding immune therapy sensitivity and resistance. Here we develop...

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Detalles Bibliográficos
Autores: Perucca, Alice, Gómez-Llonín, Andrea, Rivas, Elisa, Linares, Jenniffer, Garrido, Marta, Sallent-Aragay, Anna, Recort-Bascuas, Alba, Comerma Blesa, Laura, 1983-, Rovira, Ana, Albanell Mestres, Joan, Calon, Alexandre, Labernadie, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/72363
Acceso en línea:https://hdl.handle.net/10230/72363
http://dx.doi.org/10.1038/s41467-025-56275-1
Access Level:acceso abierto
Palabra clave:Biological techniques
Biomedical engineering
Cancer microenvironment
Interleukins
Descripción
Sumario:Immunotherapies are beneficial for a considerable proportion of cancer patients, but ineffective in others. In vitro modelling of the complex interactions between cancer cells and their microenvironment could provide a path to understanding immune therapy sensitivity and resistance. Here we develop MIRO, a fully humanised in vitro platform to model the spatial organisation of the tumour/stroma interface and its interaction with immune cells. We find that stromal barriers are associated with immune exclusion and protect cancer cells from antibody-dependent cellular cytotoxicity, elicited by targeted therapy. We demonstrate that IL2-driven immunomodulation increases immune cell velocity and spreading to overcome stromal immunosuppression and restores anti-cancer response in refractory tumours. Collectively, our study underscores the translational value of MIRO as a powerful tool for exploring how the spatial organisation of the tumour microenvironment shapes the immune landscape and influences the responses to immunomodulating therapies.