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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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.
“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]
The Results describe coculturing patient PBMCs with autologous tumor organoids, and the Discussion proposes using the platform to investigate sensitivity to immunotherapy (page numbers unavailable). The paper presents peripheral-blood cells as an alternative to tumor-infiltrating lymphocytes; it does not establish a TIL–organoid coculture platform or address phage-delivered antigens. (LLM, conf=0.88)
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- 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
- 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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