Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Krijn K Dijkstra, Chiara M Cattaneo, Fleur Weeber, Myriam Chalabi, Joris van de Haar, Lorenzo F Fanchi, Maarten Slagter, Daphne L van der Velden, Sovann Kaing, Sander Kelderman, Nienke van Rooij, Monique E van Leerdam, Annekatrien Depla, Egbert F Smit, Koen J Hartemink, Rosa de Groot, Monika C Wolkers, Norman Sachs, Petur Snaebjornsson, Kim MonkhorstJohn Haanen, Hans Clevers, Ton N Schumacher, Emile E Voest

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1586-1598.e12
JournalCell
Volume174
Issue number6
DOIs
Publication statusPublished - 6 Sep 2018

Cite this

Dijkstra, K. K., Cattaneo, C. M., Weeber, F., Chalabi, M., van de Haar, J., Fanchi, L. F., ... Voest, E. E. (2018). Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids. Cell, 174(6), 1586-1598.e12. https://doi.org/10.1016/j.cell.2018.07.009