Tumor organoid–T-cell coculture systems
Open accessAbstract
T cells are key players in cancer immunotherapy, but strategies to expand tumor-reactive cells and study their interactions with tumor cells at the level of an individual patient are limited. Here we describe the generation and functional assessment of tumor-reactive T cells based on cocultures of tumor organoids and autologous peripheral blood lymphocytes. The procedure consists of an initial coculture of 2 weeks, in which tumor-reactive T cells are first expanded in the presence of (IFNγ-stimulated) autologous tumor cells. Subsequently, T cells are evaluated for their capacity to carry out effector functions (IFNγ secretion and degranulation) after recognition of tumor cells, and their capacity to kill tumor organoids. This strategy is unique in its use of peripheral blood as a source of tumor-reactive T cells in an antigen-agnostic manner. In 2 weeks, tumor-reactive CD8+ T-cell populations can be obtained from ~33-50% of samples from patients with non-small-cell lung cancer (NSCLC) and microsatellite-instable colorectal cancer (CRC). This enables the establishment of ex vivo test systems for T-cell-based immunotherapy 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 [111]
The Introduction’s Experimental design section describes coculturing human PBMCs with autologous tumor organoids, and Applications of the protocol proposes using the system to investigate immuno-oncology drugs. Comparison with other approaches mentions tumor-derived immune cells in other coculture systems, but this paper’s protocol uses peripheral blood cells. No passage supports testing responses to phage-delivered antigens. Page numbers are not available in our copy. (LLM, conf=0.88)
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- Authors
- Cattaneo, C. M., Dijkstra, K. K., Fanchi, L. F., Kelderman, S., Kaing, S., van Rooij, N., van den Brink, S., Schumacher, T. N., & Voest, E. E.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Voest, Emile E.
- Venue
- Nature Protocols
- Published
- 2019-12-18
- Volume
- 15
- Issue
- 1
- Pages
- 15-39
- ISSN
- 1750-2799 (ISSN-L)
- 1754-2189
- PMC
- PMC7610702
- OpenAlex
- W2995460694
- Cited by
- 410
- References
- 8
- Citations by year
- 2026: 87 · 2025: 82 · 2024: 69 · 2023: 60 · 2022: 53 · 2021: 46 · 2020: 13
- FWCI
- 11.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Protocols (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- 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 organoids, tumor-reactive T cells, CD8+ T cells, T cell effector function, T cell degranulation, non-small cell lung cancer, cancer immunotherapy
- MeSH terms
- Humans, Neoplasms, Organoids, T-Lymphocytes, Coculture Techniques
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