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Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids
Open accessAbstract
Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.
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“In addition, ex vivo coculture systems utilizing human peripheral blood mononuclear cells or tumor-infiltrating lymphocytes cocultured with patient-derived organoids provide valuable platforms to interrogate human-specific immune responses to phage-delivered antigens or immunotherapies [111–113]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [112]
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Shelkey, E., Dominijanni, A. J., Forsythe, S. D., Oommen, D., & Söker, S. (2022) · Royal Society of Chemistry eBooks · doi:10.1039/9781839166013-00279
Research Trends in Lung Organoids: Bibliometric Analysis and VisualizationPreprint
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"Obesity Leads to Inflammation & Inflammation is the Mother of Diseases"
Balachandar, J. C. (2023) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2023.48.007611
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Application and Relevance of Organoid/Tumoroid Models in the Context of Pediatric Solid Tumors
Ferreira, B., Peixoto, J., & Lima, J. P. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-15717-2.00011-1
Use of Organoids in Cancer: A New Therapeutic and Research Approach
Tonon, S., Martinis, E., Secco, C. D., Tosoni, L., Tomadini, G., Vitale, G., Pucillo, C. E. M., & Frossi, B. (2022) · Springer eBooks · doi:10.1007/978-3-030-80962-1_285-1
Tumor heterogeneity in glioblastoma
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Cryopreservation and utility of cancer organoids and cartilage microtissues
Shajib, M. S. (2023) · Queensland University of Technology · doi:10.5204/thesis.eprints.244762
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Transcriptome profiling reveals cuproptosis heterogeneity in triple-negative breast cancerPreprint
Song, X.-Q., Jiang, J., Sui, X.-Y., & Shao, Z. (2023) · Research Square · doi:10.21203/rs.3.rs-3724433/v1
Organoid Culture Applications: Mini Systematic Review
Efendi, R., Amar, P. K., Rahayu, R., Santoso, P., Noli, Z. A., & Maliza, R. (2023) · JURNAL BIOLOGI TROPIS · doi:10.29303/jbt.v23i4.5387
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Mechanistic and Clinical Chemoprevention
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GAS-Luc2 Reporter Cell Lines for Immune Checkpoint Drug Screening in Solid Tumors
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Patientenabgeleitete 3-D-Tumormodelle
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Current and future perspectives of xenograft models of human ovarian cancer
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Probing T-cell activation in nanoliter tumor co-cultures using membrane displacement trap arrays
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Metadata
- Authors
- Dijkstra, K. K., Cattaneo, C. M., Weeber, F., Chalabi, M., van de Haar, J., Fanchi, L. F., Slagter, M., van der Velden, D. L., Kaing, S., Kelderman, S., van Rooij, N., van Leerdam, M. E., Depla, A., Smit, E. F., Hartemink, K. J., de Groot, R., Wolkers, M. C., Sachs, N., Snaebjornsson, P., Monkhorst, K., Haanen, J., Clevers, H., Schumacher, T. N., & Voest, E. E.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Slotervaartziekenhuis (NL)
- Sanquin (NL)
- University Medical Center Utrecht (NL)
- Corresponding author
- Voest, Emile E.
- ORCID
- Dijkstra, Krijn K.
- Cattaneo, Chiara M.
- Weeber, Fleur
- Chalabi, Myriam
- van de Haar, Joris
- Fanchi, Lorenzo F.
- Slagter, Maarten
- van Rooij, Nienke
- van Leerdam, Monique E.
- Smit, Egbert F.
- Hartemink, Koen J.
- de Groot, Rosa
- Wolkers, Monika C.
- Sachs, Norman
- Monkhorst, Kim
- Haanen, John
- Clevers, Hans
- Schumacher, Ton N.
- Voest, Emile E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 174
- Issue
- 6
- Pages
- 1586-1598.e12
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6558289
- OpenAlex
- W2885650843
- Cited by
- 1,135
- References
- 47
- Citations by year
- 2026: 172 · 2025: 175 · 2024: 143 · 2023: 154 · 2022: 144 · 2021: 168 · 2020: 106 · 2019: 62 · 2018: 10
- FWCI
- 37.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- NWO Gravitation Program (NWO (2012-2022)
- KWF (HUBR2014-7006)
- KWF Queen Wilhelmina (NKI 2013-6122)
- ERC AdG SENSIT
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- tumor-reactive T cells, tumor organoids, peripheral blood lymphocytes, co-culture, personalized cancer immunotherapy, non-small cell lung cancer, epithelial cancers, T cell-mediated killing
- MeSH terms
- Aged, Carcinoma, Non-Small-Cell Lung, Female, Humans, Interferon-gamma, Leukocytes, Mononuclear, Lung Neoplasms, Lymphocyte Activation, Male, Middle Aged, T-Lymphocytes, Tumor Cells, Cultured, Colorectal Neoplasms, Coculture Techniques, Cell Culture Techniques, In Vitro Techniques
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