Probing the killing potency of tumor-infiltrating lymphocytes on microarrayed colorectal cancer tumoroids.

Journal

NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166

Informations de publication

Date de publication:
14 Aug 2024
Historique:
received: 28 06 2023
accepted: 19 07 2024
medline: 15 8 2024
pubmed: 15 8 2024
entrez: 14 8 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41698-024-00661-3 PMID: 39143103
pubmed: 39143103
doi: 10.1038/s41698-024-00661-3
pii: 10.1038/s41698-024-00661-3
doi:

Types de publication

Journal Article

Langues

eng

Pagination

179

Informations de copyright

© 2024. The Author(s).

Références

Emens, L. A. et al. Cancer immunotherapy: opportunities and challenges in the rapidly evolving clinical landscape. Eur. J. Cancer 81, 116–129 (2017).
doi: 10.1016/j.ejca.2017.01.035 pubmed: 28623775
Wieder, T., Eigentler, T., Brenner, E. & Röcken, M. Immune checkpoint blockade therapy. J. Allergy Clin. Immunol. 142, 1403–1414 (2018).
doi: 10.1016/j.jaci.2018.02.042 pubmed: 29596939
Jenkins, R. W., Barbie, D. A. & Flaherty, K. T. Mechanisms of resistance to immune checkpoint inhibitors. Br. J. Cancer 118, 9–16 (2018).
doi: 10.1038/bjc.2017.434 pubmed: 29319049 pmcid: 5765236
Sahin, I. H. et al. Immune checkpoint inhibitors for the treatment of MSI-H/MMR-D colorectal cancer and a perspective on resistance mechanisms. Br. J. Cancer 121, 809–818 (2019).
doi: 10.1038/s41416-019-0599-y pubmed: 31607751 pmcid: 6889302
Aref, A. R. et al. 3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade. Lab Chip 18, 3129–3143 (2018).
doi: 10.1039/C8LC00322J pubmed: 30183789 pmcid: 6274590
Neal, J. T. et al. Organoid modeling of the tumor immune microenvironment. Cell 175, 1972–1988.e1916 (2018).
doi: 10.1016/j.cell.2018.11.021 pubmed: 30550791 pmcid: 6656687
Yuki, K., Cheng, N., Nakano, M. & Kuo, C. J. Organoid models of tumor immunology. Trends Immunol. 41, 652–664 (2020).
doi: 10.1016/j.it.2020.06.010 pubmed: 32654925 pmcid: 7416500
van de Wetering, M. et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933–945 (2015).
doi: 10.1016/j.cell.2015.03.053 pubmed: 25957691 pmcid: 6428276
Ooft, S. N. et al. Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients. Sci. Transl. Med. 11, https://doi.org/10.1126/scitranslmed.aay2574 (2019).
Vlachogiannis, G. et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 359, 920–926 (2018).
doi: 10.1126/science.aao2774 pubmed: 29472484 pmcid: 6112415
Sveen, A., Kopetz, S. & Lothe, R. A. Biomarker-guided therapy for colorectal cancer: strength in complexity. Nat. Rev. Clin. Oncol. 17, 11–32 (2020).
doi: 10.1038/s41571-019-0241-1 pubmed: 31289352
Vonderheide, R. H. CD40 agonist antibodies in cancer immunotherapy. Annu. Rev. Med. 71, 47–58 (2020).
doi: 10.1146/annurev-med-062518-045435 pubmed: 31412220
Bever, K. M. & Le, D. T. DNA repair defects and implications for immunotherapy. J. Clin. Investig. 128, 4236–4242 (2018).
doi: 10.1172/JCI122010 pubmed: 30272580 pmcid: 6159999
Lorenzo-Martín, L. F. et al. Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo. Nature https://doi.org/10.1038/s41586-024-07330-2 (2024).
Lorenzo-Martín, L. F. et al. Patient-derived mini-colons enable long-term modeling of tumor-microenvironment complexity. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02301-4 (2024).
Broguiere, N. et al. Dissection and reconstruction of the colorectal cancer tumor microenvironment. bioRxiv 2023.11.01.565169; https://doi.org/10.1101/2023.11.01.565169 (2023)
Fujii, M. et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 18, 827–838 (2016).
doi: 10.1016/j.stem.2016.04.003 pubmed: 27212702
Brandenberg, N. et al. High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays. Nat. Biomed. Eng. 4, 863–874 (2020).
doi: 10.1038/s41551-020-0565-2 pubmed: 32514094

Auteurs

Devanjali Dutta (D)

Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Genmab B.V., Utrecht, Netherlands.

L Francisco Lorenzo-Martín (LF)

Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
ORCID: 0000-0003-4717-9338

François Rivest (F)

Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Lunaphore, Tolochenaz, Switzerland.

Nicolas Broguiere (N)

Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
ORCID: 0000-0001-9934-4505

Lucie Tillard (L)

Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Simone Ragusa (S)

Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Molecular Partners AG, Zürich, Switzerland.

Nathalie Brandenberg (N)

Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
DOPPL, Lausanne, Switzerland.

Sylke Höhnel (S)

Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
SUN bioscience, Lausanne, Switzerland.
ORCID: 0000-0001-8449-1692

Damien Saugy (D)

The Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Sylvie Rusakiewicz (S)

The Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Krisztian Homicsko (K)

The Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Ludwig Institute for Cancer Research, Lausanne, Switzerland.

George Coukos (G)

Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Ludwig Institute for Cancer Research, Lausanne, Switzerland.

Matthias P Lutolf (MP)

Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. matthias.lutolf@epfl.ch.
Institute of Human Biology (IHB), Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland. matthias.lutolf@epfl.ch.

Classifications MeSH