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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月3日

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  • 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

摘要

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.