Studies of tumor immunology will gain from coculture of tumor organoids and peripheral blood cells.
It is common these days to cite the lack of an immune component as a limiting factor in organoid culture. A recent study from the group of Emile Voest at the Netherlands Cancer Institute shows a different situation for organoids derived from human cancer tissue. The scientists demonstrate that tumor organoids—3D in vitro–cultured primary tumor cells that resemble the in vivo tumor—can recruit tumor-specific T cells from peripheral blood.
The exciting field of immunotherapy, in which autologous ex vivo–expanded T cells are used to treat cancer, must contend with the fact that many people do not respond well to the therapy. The reasons for this are many and complex; models are needed to study tumor–immune interaction.
In their recent work, Voest and colleagues built such a model for epithelial cancers. Using cells from people with colorectal cancer and non-small-cell lung cancer, they established tumor organoids and then used those cultures (with appropriate adjuvants) to stimulate peripheral blood lymphocytes from the same patients. After two weeks, the scientists reported an expansion of CD8+ tumor-reactive T cell populations in about 30% of cases. The coculture model can both expand existing pools of tumor-responsive T cells and amplify clones that were undetectable before stimulation. In a subset of cases, Voest and colleagues tested the specificity of the CD8+ T cells, and found that most were activated in response to tumor but not normal organoids. Finally, in short-term (three-day) functional studies, they found that recruited CD8+ T cells reduce the survival of tumor, but not healthy, organoids; this effect can be blocked by antibodies to the major histocompatibility complex.
No doubt this coculture model will be investigated as a platform for personalized medicine, as a way to either expand tumor-reactive T cells or predict or monitor a patient’s response to therapy. But it is also a promising tool for studies of tumor–immune interaction in varied cancers and genetic backgrounds, and could improve our understanding of this critical process.
Dijkstra, K. K. et al. Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids. Cell 174, 1586–1598 (2018).
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de Souza, N. A model for tumor–immune interaction. Nat Methods 15, 762 (2018). https://doi.org/10.1038/s41592-018-0165-1