A gut-on-a-chip incorporating human faecal samples and peristalsis predicts responses to immune checkpoint inhibitors for melanoma
Patient responses to immune checkpoint inhibitors can be influenced by the gastrointestinal microbiome. Mouse models can be used to study microbiome-host crosstalk, yet their utility is constrained by substantial anatomical, functional, immunological and microbial differences between mice and humans. Here we show that a gut-on-a-chip system mimicking the architecture and functionality of the human intestine by including faecal microbiome and peristaltic-like movements recapitulates microbiome-host interactions and predicts responses to immune checkpoint inhibitors in patients with melanoma. The system is composed of a vascular channel seeded with human microvascular endothelial cells and an intestinal channel with intestinal organoids derived from human induced pluripotent stem cells, with the two channels separated by a collagen matrix. By incorporating faecal samples from patients with melanoma into the intestinal channel and by performing multiomic analyses, we uncovered epithelium-specific biomarkers and microbial factors that correlate with clinical outcomes in patients with melanoma and that the microbiome of non-responders has a reduced ability to buffer cellular stress and self-renew. The gut-on-a-chip model may help identify prognostic biomarkers and therapeutic targets.
Authors
- Hariam Raji (ORCID: https://orcid.org/0000-0002-2705-8857)
- Luigi Nezi (ORCID: https://orcid.org/0000-0002-4670-7656)
- Serena Galié (ORCID: https://orcid.org/0000-0003-4431-3140)
- Carlotta Catozzi (ORCID: https://orcid.org/0000-0002-1028-1489)
- Andrea Vignati (ORCID: https://orcid.org/0000-0001-7555-0072)
- Pier Francesco Ferrucci (ORCID: https://orcid.org/0000-0001-6255-5851)
- Marco Rasponi (ORCID: https://orcid.org/0000-0002-2904-8652)
- Jennifer Ann Wargo (ORCID: https://orcid.org/0000-0003-3438-7576)
- Alessandro Cordiale (ORCID: https://orcid.org/0000-0003-2918-7131)
- Paola Occhetta (ORCID: https://orcid.org/0000-0002-5758-2019)
- Michela Deleidi (ORCID: https://orcid.org/0000-0003-0357-0124)
- Emilia Cocorocchio (ORCID: https://orcid.org/0000-0003-1184-6426)
- Nicola Segata (ORCID: https://orcid.org/0000-0002-1583-5794)
- Bianca Ionela Slivinschi
- Teresa Manzo (ORCID: https://orcid.org/0000-0001-8552-3625)
- Punit Tyagi
- Mattia Ballerini (ORCID: https://orcid.org/0009-0009-1934-9644)
- Amir Nabinejad (ORCID: https://orcid.org/0000-0003-3276-1368)
- Andrey Morgun (ORCID: https://orcid.org/0000-0002-8924-6108)
- Angeli Dominique Macandog
- Karol K. Kugiejko
- Martina Freisa
Institutions
- Oregon State University (US)
- The University of Texas MD Anderson Cancer Center (US)
- Inserm (FR)
- University of Trento (IT)
- Université Paris Cité (FR)
- MultiMedica (IT)
- Humanitas Gavazzeni (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- University of Turin (IT)
- European Institute of Oncology (IT)
- Politecnico di Milano (IT)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2025-02-12
- DOI
- https://doi.org/10.1038/s41551-024-01318-z
- Citations
- 44
- Primary Topic
- 3D Printing in Biomedical Research
- Type
- article
- Field-Weighted Citation Impact
- 29.66
Funders
- Worldwide Cancer Research
- Fondazione Istituto Europeo di Oncologia e Centro Cardiologico Monzino
- European Commission
- Ministero della Salute
- Fondation de France
- Fondazione Umberto Veronesi
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health
- Horizon 2020 Framework Programme