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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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
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/219463
Acesso em linha:https://hdl.handle.net/2445/219463
Access Level:acceso abierto
Palavra-chave:Tumors
Cultiu cel·lular
Immunoteràpia
Càncer
Cell culture
Immunotheraphy
Cancer
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spelling Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testingPerucca, 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, AnnaTumorsCultiu cel·lularImmunoteràpiaCàncerTumorsCell cultureImmunotheraphyCancerImmunotherapies 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.Nature Publishing Group2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/219463Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41467-025-56275-1Nature Communications, 2025, vol. 16, num.1https://doi.org/10.1038/s41467-025-56275-1cc-by (c) Perucca, A. et al., 2025http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2194632026-05-27T06:46:51Z
dc.title.none.fl_str_mv Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
title Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
spellingShingle Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
Perucca, Alice
Tumors
Cultiu cel·lular
Immunoteràpia
Càncer
Tumors
Cell culture
Immunotheraphy
Cancer
title_short Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
title_full Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
title_fullStr Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
title_full_unstemmed Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
title_sort Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
dc.creator.none.fl_str_mv 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
author Perucca, Alice
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tumors
Cultiu cel·lular
Immunoteràpia
Càncer
Tumors
Cell culture
Immunotheraphy
Cancer
topic Tumors
Cultiu cel·lular
Immunoteràpia
Càncer
Tumors
Cell culture
Immunotheraphy
Cancer
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/219463
url https://hdl.handle.net/2445/219463
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-025-56275-1
Nature Communications, 2025, vol. 16, num.1
https://doi.org/10.1038/s41467-025-56275-1
dc.rights.none.fl_str_mv cc-by (c) Perucca, A. et al., 2025
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Perucca, A. et al., 2025
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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