Cell
Volume 174, Issue 6, 6 September 2018, Pages 1586-1598.e12
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Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

https://doi.org/10.1016/j.cell.2018.07.009Get rights and content
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Highlights

  • Induction of tumor-reactive T cells by co-culture of PBMCs and tumor organoids

  • Induced T cell populations do not recognize healthy organoids or tissue

  • This platform can be used to assess the efficiency of T-cell-mediated tumor killing

Summary

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.

Keywords

organoids
immunotherapy
adoptive cell transfer
immune checkpoint blockade
colorectal cancer
non-small cell lung cancer
mismatch repair deficient
microsatellite instable
T cell

Cited by (0)

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These authors contributed equally

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These authors contributed equally

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Present address: Vertex Pharmaceuticals Inc., San Diego, CA 92121, USA

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Lead Contact