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 Monkhorst; John Haanen; Hans Clevers; Ton N Schumacher; Emile E Voest

doi:10.1016/j.cell.2018.07.009

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

698 Citations (Scopus)

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 language	English
Pages (from-to)	1586-1598.e12
Journal	Cell
Volume	174
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2018.07.009
Publication status	Published - 06 Sept 2018

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10.1016/j.cell.2018.07.009

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Dijkstra, K. K., Cattaneo, C. M., Weeber, F., Chalabi, M., van de Haar, J., Fanchi, L. F., Slagter, M., van der Velden, D. L., Kaing, S., Kelderman, S., van Rooij, N., van Leerdam, M. E., Depla, A., Smit, E. F., Hartemink, K. J., de Groot, R., Wolkers, M. C., Sachs, N., Snaebjornsson, P., ... 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

@article{68305f9fe9b348669a1a349268ac7c78,

title = "Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids",

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.",

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

year = "2018",

month = sep,

day = "6",

doi = "10.1016/j.cell.2018.07.009",

language = "English",

volume = "174",

pages = "1586--1598.e12",

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Dijkstra, KK, Cattaneo, CM, Weeber, F, Chalabi, M, van de Haar, J, Fanchi, LF, Slagter, M, van der Velden, DL, Kaing, S, Kelderman, S, van Rooij, N, van Leerdam, ME, Depla, A, Smit, EF, Hartemink, KJ, de Groot, R, Wolkers, MC, Sachs, N, Snaebjornsson, P, Monkhorst, K, Haanen, J, Clevers, H, Schumacher, TN & Voest, EE 2018, 'Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids', Cell, vol. 174, no. 6, pp. 1586-1598.e12. https://doi.org/10.1016/j.cell.2018.07.009

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

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 -

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

Abstract

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