Perucca, AliceGómez Llonín, AndreaMañé Benach, OriolHallopeau, ClementRivas, Elisa I.Linares, JennifferGarrido, MartaSallent Aragay, AnnaGolde, TomColombelli, JulienDalaka, EleniLinacero, JudithCazorla, MarinaGalan, TeresaPastor Viel, JordiBadenas, XavierRecort-Bascuas, A.Comerma, LauraFernández Nogueira, PatriciaRovira, AnaRoca-Cusachs Soulere, PereAlbanell Mestres, JoanTrepat Guixer, XavierCalon, AlexandreLabernadie, Anna2025-03-052025-03-052025-12-012041-1723https://hdl.handle.net/2445/219463Immunotherapies 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.20 p.application/pdfengcc-by (c) Perucca, A. et al., 2025http://creativecommons.org/licenses/by/4.0/TumorsCultiu cel·lularImmunoteràpiaCàncerTumorsCell cultureImmunotheraphyCancerinfo:eu-repo/semantics/article7573542025-03-05info:eu-repo/semantics/openAccess672652639900918