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

Alice Perucca, Andrea Gómez Llonín, Oriol Mañé Benach, Clement Hallopeau, Elisa I. Rivas, Jenniffer Linares, Marta Garrido, Anna Sallent-Aragay, Tom Golde, Julien Colombelli, Eleni Dalaka, Judith Linacero, Marina Cazorla, Teresa Galan, Jordi Pastor Viel, Xavier Badenas, Alba Recort-Bascuas, Laura Comerma, Patricia Fernandez-Nogueira, Ana Rovira, Pere Roca-Cusachs, Joan Albanell, Xavier Trepat (), Alexandre Calon () and Anna Labernadie ()
Additional contact information
Alice Perucca: The Barcelona Institute for Science and Technology (BIST)
Andrea Gómez Llonín: Hospital del Mar Research Institute (HMRIB)
Oriol Mañé Benach: The Barcelona Institute for Science and Technology (BIST)
Clement Hallopeau: The Barcelona Institute for Science and Technology (BIST)
Elisa I. Rivas: Hospital del Mar Research Institute (HMRIB)
Jenniffer Linares: Hospital del Mar Research Institute (HMRIB)
Marta Garrido: Hospital del Mar Research Institute (HMRIB)
Anna Sallent-Aragay: Hospital del Mar Research Institute (HMRIB)
Tom Golde: The Barcelona Institute for Science and Technology (BIST)
Julien Colombelli: Barcelona Institute of Science and Technology (BIST)
Eleni Dalaka: The Barcelona Institute for Science and Technology (BIST)
Judith Linacero: The Barcelona Institute for Science and Technology (BIST)
Marina Cazorla: The Barcelona Institute for Science and Technology (BIST)
Teresa Galan: The Barcelona Institute for Science and Technology (BIST)
Jordi Pastor Viel: Universitat de Barcelona
Xavier Badenas: Universitat de Barcelona
Alba Recort-Bascuas: Hospital del Mar Research Institute (HMRIB)
Laura Comerma: Hospital del Mar Research Institute (HMRIB)
Patricia Fernandez-Nogueira: Universitat de Barcelona
Ana Rovira: Hospital del Mar Research Institute (HMRIB)
Pere Roca-Cusachs: The Barcelona Institute for Science and Technology (BIST)
Joan Albanell: Hospital del Mar Research Institute (HMRIB)
Xavier Trepat: The Barcelona Institute for Science and Technology (BIST)
Alexandre Calon: Hospital del Mar Research Institute (HMRIB)
Anna Labernadie: The Barcelona Institute for Science and Technology (BIST)

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-56275-1

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