Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell, 2018-09, Vol.174 (6), p.1586-1598.e12

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. [Display omitted] •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 A modified patient-derived tumor organoids system allows the expansion of tumor-specific T cells from blood for personalized analysis of their anti-cancer properties.