Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56275-1 |
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| author | 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 Anna Labernadie |
| author_facet | 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 Anna Labernadie |
| author_sort | Alice Perucca |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9fd19474890a48688f798c7bbb26d3c1 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9fd19474890a48688f798c7bbb26d3c12025-02-09T12:46:26ZengNature PortfolioNature Communications2041-17232025-02-0116112010.1038/s41467-025-56275-1Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testingAlice Perucca0Andrea Gómez Llonín1Oriol Mañé Benach2Clement Hallopeau3Elisa I. Rivas4Jenniffer Linares5Marta Garrido6Anna Sallent-Aragay7Tom Golde8Julien Colombelli9Eleni Dalaka10Judith Linacero11Marina Cazorla12Teresa Galan13Jordi Pastor Viel14Xavier Badenas15Alba Recort-Bascuas16Laura Comerma17Patricia Fernandez-Nogueira18Ana Rovira19Pere Roca-Cusachs20Joan Albanell21Xavier Trepat22Alexandre Calon23Anna Labernadie24Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Cancer Research Program, Hospital del Mar Research Institute (HMRIB)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Cancer Research Program, Hospital del Mar Research Institute (HMRIB)Cancer Research Program, Hospital del Mar Research Institute (HMRIB)Cancer Research Program, Hospital del Mar Research Institute (HMRIB)Cancer Research Program, Hospital del Mar Research Institute (HMRIB)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Unitat de Tecnologia Mecànica, Centres Científics i Tecnològics, Universitat de BarcelonaUnitat de Tecnologia Mecànica, Centres Científics i Tecnològics, Universitat de BarcelonaCancer Research Program, Hospital del Mar Research Institute (HMRIB)Cancer Research Program, Hospital del Mar Research Institute (HMRIB)Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaCancer Research Program, Hospital del Mar Research Institute (HMRIB)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Cancer Research Program, Hospital del Mar Research Institute (HMRIB)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)Cancer Research Program, Hospital del Mar Research Institute (HMRIB)Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST)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.https://doi.org/10.1038/s41467-025-56275-1 |
| spellingShingle | 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 Anna Labernadie Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing Nature Communications |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41467-025-56275-1 |
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