Modular engineered colorectal tumor microenvironments for immuno-oncology research and drug development
- 1Institute of Human Biology (IHB), Roche Pharma Research and Early Development, Basel, Switzerland
Abstract
The development of cancer immunotherapies is hindered by the lack of human-relevant models that accurately translate to patient outcomes. We combine patient-derived colorectal tumor organoids (PDOs) and cancer-associated fibroblasts (CAFs) into floating extracellular matrix drops to form miniature colorectal tumors. These SHaking Organoid CO-cultures (SHOCOs) reproducibly capture key features of the tumor microenvironment (TME), including physiologically relevant ECM, hypoxic regions, and a diversified stromal compartment that captures primary CAF states. Compared with traditional PDO-based co-culture models, SHOCOs maintain immune cells in numbers, states and functional interactions that more closely reflect the physiological tumor microenvironment. The modularity of the system allowed controlled simulation of diverse patient tumor archetypes, and defining how TME components shape therapy response. Immune-rich SHOCOs treated with T-cell bispecific antibodies exhibited robust anti-tumor responses that were stronger and more rapid than their PDO-based counterparts. Stroma-rich tumors, on the other hand, diminished therapy responses by physically hindering both immune cell recruitment and limiting antibody penetration. Thus, SHOCOs enable the construction of modular tumor microenvironments, providing a versatile platform to dissect immune and stromal tumor biology and to catalyze the discovery of novel therapeutic approaches.
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BibTeX
@misc{filip2026modular,
title = {{Modular engineered colorectal tumor microenvironments for immuno-oncology research and drug development}},
author = {A. M. Filip and B. Lavickova and A. Herault and I. Cubela and B. Ehret and E. Danenberg and M. Daniel and S. Chevrier and M. Coto-Llerena and G. Protti and S. Muller and S. Jansen and K. Kromer and M. F. Harter and S. Tsiepa and I. Lukonin and W. Jin and P. Jean-Mairet and F. Cremasco and S. Colombetti and L. Cabon and N. Gjorevski},
howpublished = {bioRxiv},
year = {2026},
month = jun,
doi = {10.64898/2026.06.02.729459},
url = {https://www.biorxiv.org/content/10.64898/2026.06.02.729459v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Modular engineered colorectal tumor microenvironments for immuno-oncology research and drug development
AU - A. M. Filip
AU - B. Lavickova
AU - A. Herault
AU - I. Cubela
AU - B. Ehret
AU - E. Danenberg
AU - M. Daniel
AU - S. Chevrier
AU - M. Coto-Llerena
AU - G. Protti
AU - S. Muller
AU - S. Jansen
AU - K. Kromer
AU - M. F. Harter
AU - S. Tsiepa
AU - I. Lukonin
AU - W. Jin
AU - P. Jean-Mairet
AU - F. Cremasco
AU - S. Colombetti
AU - L. Cabon
AU - N. Gjorevski
PY - 2026
DA - 2026/06/02
PB - bioRxiv
DO - 10.64898/2026.06.02.729459
UR - https://www.biorxiv.org/content/10.64898/2026.06.02.729459v2
AB - The development of cancer immunotherapies is hindered by the lack of human-relevant models that accurately translate to patient outcomes. We combine patient-derived colorectal tumor organoids (PDOs) and cancer-associated fibroblasts (CAFs) into floating extracellular matrix drops to form miniature colorectal tumors. These SHaking Organoid CO-cultures (SHOCOs) reproducibly capture key features of the tumor microenvironment (TME), including physiologically relevant ECM, hypoxic regions, and a diversified stromal compartment that captures primary CAF states. Compared with traditional PDO-based co-culture models, SHOCOs maintain immune cells in numbers, states and functional interactions that more closely reflect the physiological tumor microenvironment. The modularity of the system allowed controlled simulation of diverse patient tumor archetypes, and defining how TME components shape therapy response. Immune-rich SHOCOs treated with T-cell bispecific antibodies exhibited robust anti-tumor responses that were stronger and more rapid than their PDO-based counterparts. Stroma-rich tumors, on the other hand, diminished therapy responses by physically hindering both immune cell recruitment and limiting antibody penetration. Thus, SHOCOs enable the construction of modular tumor microenvironments, providing a versatile platform to dissect immune and stromal tumor biology and to catalyze the discovery of novel therapeutic approaches.
ER -