| Literature DB >> 30100188 |
Krijn K Dijkstra1, Chiara M Cattaneo1, Fleur Weeber1, Myriam Chalabi2, Joris van de Haar1, Lorenzo F Fanchi1, Maarten Slagter1, Daphne L van der Velden1, Sovann Kaing1, Sander Kelderman1, Nienke van Rooij1, Monique E van Leerdam3, Annekatrien Depla4, Egbert F Smit5, Koen J Hartemink6, Rosa de Groot7, Monika C Wolkers8, Norman Sachs9, Petur Snaebjornsson10, Kim Monkhorst10, John Haanen1, Hans Clevers11, Ton N Schumacher12, Emile E Voest13.
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.Entities:
Keywords: T cell; adoptive cell transfer; colorectal cancer; immune checkpoint blockade; immunotherapy; microsatellite instable; mismatch repair deficient; non-small cell lung cancer; organoids
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Year: 2018 PMID： 30100188 PMCID： PMC6558289 DOI： 10.1016/j.cell.2018.07.009
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582