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Cell. 2018 Sep 6;174(6):1586-1598.e12. doi: 10.1016/j.cell.2018.07.009. Epub 2018 Aug 9.

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

Author information

1
Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands.
2
Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands; Department of Gastroenterologic Oncology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands.
3
Department of Gastroenterologic Oncology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands.
4
Department of Gastroenterology and Hepatology, EC Slotervaart Hospital, 1066 CX Amsterdam, the Netherlands.
5
Department of Thoracic Oncology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands.
6
Department of Surgery, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands.
7
Department of Hematopoeisis, Sanquin Research, 1066 CX Amsterdam, the Netherlands.
8
Department of Hematopoeisis, Sanquin Research, 1066 CX Amsterdam, the Netherlands; Landsteiner Laboratory, Amsterdam Medical Center, 1105 AZ Amsterdam, the Netherlands.
9
Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
10
Department of Pathology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands.
11
Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands; Oncode Institute, the Netherlands.
12
Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands; Oncode Institute, the Netherlands.
13
Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands. Electronic address: e.voest@nki.nl.

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.

KEYWORDS:

T cell; adoptive cell transfer; colorectal cancer; immune checkpoint blockade; immunotherapy; microsatellite instable; mismatch repair deficient; non-small cell lung cancer; organoids

PMID:
30100188
PMCID:
PMC6558289
DOI:
10.1016/j.cell.2018.07.009
[Indexed for MEDLINE]
Free PMC Article

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