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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Authors: Perucca, Alice, Gómez-Llonín, Andrea, Rivas, Elisa, Linares, Jenniffer, Garrido, Marta, Sallent-Aragay, Anna, Recort-Bascuas, Alba, Comerma Blesa, Laura, 1983-, Rovira, Ana, Albanell Mestres, Joan, Calon, Alexandre, Labernadie, Anna
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/72363
Online Access:https://hdl.handle.net/10230/72363
http://dx.doi.org/10.1038/s41467-025-56275-1
Access Level:Open access
Keyword:Biological techniques
Biomedical engineering
Cancer microenvironment
Interleukins
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oai_identifier_str oai:recercat.cat:10230/72363
network_acronym_str ES
network_name_str España
repository_id_str
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
Biological techniques
Biomedical engineering
Cancer microenvironment
Interleukins
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
Rivas, Elisa
Linares, Jenniffer
Garrido, Marta
Sallent-Aragay, Anna
Recort-Bascuas, Alba
Comerma Blesa, Laura, 1983-
Rovira, Ana
Albanell Mestres, Joan
Calon, Alexandre
Labernadie, Anna
author Perucca, Alice
author_facet Perucca, Alice
Gómez-Llonín, Andrea
Rivas, Elisa
Linares, Jenniffer
Garrido, Marta
Sallent-Aragay, Anna
Recort-Bascuas, Alba
Comerma Blesa, Laura, 1983-
Rovira, Ana
Albanell Mestres, Joan
Calon, Alexandre
Labernadie, Anna
author_role author
author2 Gómez-Llonín, Andrea
Rivas, Elisa
Linares, Jenniffer
Garrido, Marta
Sallent-Aragay, Anna
Recort-Bascuas, Alba
Comerma Blesa, Laura, 1983-
Rovira, Ana
Albanell Mestres, Joan
Calon, Alexandre
Labernadie, Anna
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biological techniques
Biomedical engineering
Cancer microenvironment
Interleukins
topic Biological techniques
Biomedical engineering
Cancer microenvironment
Interleukins
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
2026
2026
2026
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/10230/72363
http://dx.doi.org/10.1038/s41467-025-56275-1
url https://hdl.handle.net/10230/72363
http://dx.doi.org/10.1038/s41467-025-56275-1
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature Communications. 2025;16(1):1279
info:eu-repo/grantAgreement/ES/3PE/PID2021-128635NB-I00
info:eu-repo/grantAgreement/ES/3PE/PID2022-142672NB-I00
info:eu-repo/grantAgreement/EC/H2020/883739
info:eu-repo/grantAgreement/EC/H2020/731957
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testingPerucca, AliceGómez-Llonín, AndreaRivas, ElisaLinares, JennifferGarrido, MartaSallent-Aragay, AnnaRecort-Bascuas, AlbaComerma Blesa, Laura, 1983-Rovira, AnaAlbanell Mestres, JoanCalon, AlexandreLabernadie, AnnaBiological techniquesBiomedical engineeringCancer microenvironmentInterleukinsImmunotherapies 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.We thank S. Usieto, S. Menendez Romero, D. Zafra Puerta, A. Menendez, D. Izquierdo Garcia, C. Rols, J. Durand for their technical assistance. A.L. acknowledges funding from “La Caixa” Banking Foundation (LCF/BQ/PR18/11640001) and from the Spanish Ministry for Science and Innovation MICIU/AEI /10.13039/501100011033 and “ERDF-EU A way of making Europe”, (PID2021-128635NB-I00), and “ESF Investing in your future”, (RYC2020/029736/I). This work was also supported by grants from Instituto de Salud Carlos III (ISCIII) co-funded by the European Union (EU) (PI17/00211, CP16/00151, PI20/00011; Spanish Ministry of Economy and Competitiveness) to A.C. A.C. is the recipient of Miguel Servet research contracts from Instituto de Salud Carlos III co-funded by the European Union (MS16/00151, CPII21/00012). J.A. acknowledges funding from the Generalitat de Catalunya (AGAUR 2021 SGR 00776), the CIBERONC (CB16/12/00241), and the ISCIII co-funded by the EU (PI21/00002). This work was also supported by the Plan de Recuperación, Transformación y Resiliencia (CNS2023-145267) co-funded by the European Union to A.C. P.R.-C. acknowledges funding from the Spanish Ministry of Science and Innovation (PID2022-142672NB-I00), the European Research Council (AdG 101097753), the Generalitat de Catalunya (2017-SGR-1602), and the prize ‘ICREA Academia’ for excellence in research. X.T. acknowledges funding from the Generalitat de Catalunya (AGAUR SGR-2017-01602), the CERCA Programme, the Spanish Ministry for Science and Innovation MICCINN/FEDER (PID2021-128635NB-I00 MCIN/AEI/ 10.13039/501100011033 and “ERDF-EU A way of making Europe”), European Research Council (Adv-883739), Fundació la Marató de TV3 (project 201903-30-31-32), European Commission (H2020-FETPROACT-01-2016-731957), La Caixa Foundation (LCF/PR/HR20/52400004 and ID 100010434 under the agreement LCF/PR/HR20/52400004); IBEC and IRB are recipient of a Severo Ochoa Award of Excellence from the MINECO. This work was also supported by Grant PT20/00023, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, and the “Xarxa de Bancs de tumors” sponsored by Pla Director d’Oncologia de Catalunya (XBTC).Nature Research2026202620252026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/10230/72363http://dx.doi.org/10.1038/s41467-025-56275-1reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNature Communications. 2025;16(1):1279info:eu-repo/grantAgreement/ES/3PE/PID2021-128635NB-I00info:eu-repo/grantAgreement/ES/3PE/PID2022-142672NB-I00info:eu-repo/grantAgreement/EC/H2020/883739info:eu-repo/grantAgreement/EC/H2020/731957© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/723632026-05-29T05:05:01Z
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