Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
Alice Perucca, Andrea Gómez Llonín, Oriol Mañé Benach, Clément Hallopeau, Elisa Rivas, Jenniffer Linares, Marta Garrido, Anna Sallent-Aragay, Tom Golde, Julien Colombelli, Eleni Dalaka, Judith Linacero, Marina Cazorla, Teresa Galán, Jordi Pastor Viel, Xavier Badenas, Alba Recort-Bascuas, Laura Comerma, Patricia Fernández‐Nogueira, Ana Rovira, Pere Roca‐Cusachs, Joan Albanell, Xavier Trepat, Alexandre Calon, Anna Labernadie
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. Modelling the tumour immune microenvironment in vitro is a valuable tool to test immunotherapy efficiency but capturing its complexity is challenging. Here authors present a fully humanised in vitro platform representing tumour/stroma interface and demonstrate how modulation by IL2 may allow immune cells to overcome stromal barriers.