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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Aug 14

PMID 30100188

Citations 495

Authors

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 Monkhorst

John Haanen

Hans Clevers

Ton N Schumacher

Emile E Voest

Affiliations

Soon will be listed here.

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.

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