Abstract

Immunotherapy has emerged as a new standard of care for certain cancer patients with specific cellular and molecular makeups. However, there is still an unmet need for ex vivo models able to readily assess the effectiveness of immunotherapeutic treatments in a high-throughput and patient-specific manner. To address this issue, we have developed a microarrayed system of patient-derived tumoroids with recreated immune microenvironments that are optimized for the high-content evaluation of tumor-infiltrating lymphocyte functionality. Here we show that this system offers unprecedented opportunities to evaluate tumor immunogenicity, characterize the response to immunomodulators, and explore novel approaches for personalized immuno-oncology.

Details

Title
Probing the killing potency of tumor-infiltrating lymphocytes on microarrayed colorectal cancer tumoroids
Author
Dutta, Devanjali 1 ; Lorenzo-Martín, L. Francisco 2   VIAFID ORCID Logo  ; Rivest, François 3 ; Broguiere, Nicolas 2   VIAFID ORCID Logo  ; Tillard, Lucie 2 ; Ragusa, Simone 4 ; Brandenberg, Nathalie 5 ; Höhnel, Sylke 6   VIAFID ORCID Logo  ; Saugy, Damien 7 ; Rusakiewicz, Sylvie 7 ; Homicsko, Krisztian 8 ; Coukos, George 9 ; Lutolf, Matthias P. 10 

1  École Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000 0001 2183 9049); Genmab B.V., Utrecht, Netherlands (GRID:grid.466767.2) (ISNI:0000 0004 0620 3167) 
2  École Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000 0001 2183 9049) 
3  École Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000 0001 2183 9049); Lunaphore, Tolochenaz, Switzerland (GRID:grid.5333.6) 
4  École Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000 0001 2183 9049); Molecular Partners AG, Zürich, Switzerland (GRID:grid.509730.8) 
5  École Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000 0001 2183 9049); DOPPL, Lausanne, Switzerland (GRID:grid.5333.6) 
6  École Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000 0001 2183 9049); SUN bioscience, Lausanne, Switzerland (GRID:grid.5333.6) 
7  École Polytechnique Fédérale de Lausanne (EPFL), The Swiss Institute for Experimental Cancer Research (ISREC), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000 0001 2183 9049) 
8  École Polytechnique Fédérale de Lausanne (EPFL), The Swiss Institute for Experimental Cancer Research (ISREC), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000 0001 2183 9049); Ludwig Institute for Cancer Research, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204) 
9  Ludwig Institute for Cancer Research, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204) 
10  École Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000 0001 2183 9049); F. Hoffmann-La Roche Ltd., Institute of Human Biology (IHB), Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, Basel, Switzerland (GRID:grid.417570.0) (ISNI:0000 0004 0374 1269) 
Pages
179
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
ISSN
2397768X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41698-024-00661-3
ProQuest document ID
3092977117
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.