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

Author

Listed:
  • Alice Perucca

    (The Barcelona Institute for Science and Technology (BIST))

  • Andrea Gómez Llonín

    (Hospital del Mar Research Institute (HMRIB)
    University of Mauritius)

  • 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)
    Hospital del Mar
    Centro de Investigación Biomédica en Red de Oncología (CIBERONC-ISCIII))

  • Patricia Fernandez-Nogueira

    (Universitat de Barcelona)

  • Ana Rovira

    (Hospital del Mar Research Institute (HMRIB)
    Centro de Investigación Biomédica en Red de Oncología (CIBERONC-ISCIII)
    Hospital del Mar)

  • Pere Roca-Cusachs

    (The Barcelona Institute for Science and Technology (BIST)
    Universitat de Barcelona)

  • Joan Albanell

    (Hospital del Mar Research Institute (HMRIB)
    Centro de Investigación Biomédica en Red de Oncología (CIBERONC-ISCIII)
    Hospital del Mar
    Universitat Pompeu Fabra)

  • Xavier Trepat

    (The Barcelona Institute for Science and Technology (BIST)
    Universitat de Barcelona
    Institucio Catalana de Recerca i Estudis Avancats (ICREA)
    Biomaterials and Nanomedicine (CIBER-BBN))

  • Alexandre Calon

    (Hospital del Mar Research Institute (HMRIB))

  • Anna Labernadie

    (The Barcelona Institute for Science and Technology (BIST)
    Centro de Investigacion Principe Felipe)

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.

Suggested Citation

  • 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 & , 2025. "Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56275-1
    DOI: 10.1038/s41467-025-56275-1
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