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

TY - JOUR

T1 - Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

AU - Dijkstra, Krijn K

AU - Cattaneo, Chiara M

AU - Weeber, Fleur

AU - Chalabi, Myriam

AU - van de Haar, Joris

AU - Fanchi, Lorenzo F

AU - Slagter, Maarten

AU - van der Velden, Daphne L

AU - Kaing, Sovann

AU - Kelderman, Sander

AU - van Rooij, Nienke

AU - van Leerdam, Monique E

AU - Depla, Annekatrien

AU - Smit, Egbert F

AU - Hartemink, Koen J

AU - de Groot, Rosa

AU - Wolkers, Monika C

AU - Sachs, Norman

AU - Snaebjornsson, Petur

AU - Monkhorst, Kim

AU - Haanen, John

AU - Clevers, Hans

AU - Schumacher, Ton N

AU - Voest, Emile E

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/9/6

Y1 - 2018/9/6

N2 - 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.

AB - 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.

U2 - 10.1016/j.cell.2018.07.009

DO - 10.1016/j.cell.2018.07.009

M3 - Article

C2 - 30100188

SN - 0092-8674

VL - 174

SP - 1586-1598.e12

JO - Cell

JF - Cell

IS - 6

ER -