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, Mañé Benach, Oriol, Hallopeau, Clement, Rivas, Elisa I., Linares, Jenniffer, Garrido, Marta, Sallent Aragay, Anna, Golde, Tom, Colombelli, Julien, Dalaka, Eleni, Linacero, Judith, Cazorla, Marina, Galan, Teresa, Pastor Viel, Jordi, Badenas, Xavier, Recort-Bascuas, A., Comerma, Laura, Fernández Nogueira, Patricia, Rovira, Ana, Roca-Cusachs Soulere, Pere, Albanell Mestres, Joan, Trepat Guixer, Xavier, Calon, Alexandre, Labernadie, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/219463
Acceso en línea:https://hdl.handle.net/2445/219463
Access Level:acceso abierto
Palabra clave:Tumors
Cultiu cel·lular
Immunoteràpia
Càncer
Cell culture
Immunotheraphy
Cancer
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.