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

Autor: Sander Kelderman, Daphne L. van der Velden, John B. A. G. Haanen, Joris van de Haar, Egbert F. Smit, Nienke van Rooij, Annekatrien Depla, Sovann Kaing, Myriam Chalabi, Lorenzo F. Fanchi, Hans Clevers, Norman Sachs, Monika C. Wolkers, Emile E. Voest, Krijn K. Dijkstra, Monique E. van Leerdam, Maarten Slagter, Ton N. Schumacher, Fleur Weeber, Petur Snaebjornsson, Chiara M Cattaneo, Koen J. Hartemink, Kim Monkhorst, Rosa de Groot
Přispěvatelé: Pulmonary medicine, CCA - Cancer biology and immunology, AII - Cancer immunology, Surgery, Hubrecht Institute for Developmental Biology and Stem Cell Research, Radiology and Nuclear Medicine, Landsteiner Laboratory
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Adoptive cell transfer
Lung Neoplasms
Colorectal cancer
T cell
medicine.medical_treatment
T-Lymphocytes
mismatch repair deficient
Cell Culture Techniques
colorectal cancer
Biology
In Vitro Techniques
Lymphocyte Activation
Biochemistry
General Biochemistry
Genetics and Molecular Biology

03 medical and health sciences
Interferon-gamma
Carcinoma
Non-Small-Cell Lung

Organoid
medicine
Tumor Cells
Cultured

Humans
Lung cancer
adoptive cell transfer
non-small cell lung cancer
organoids
Aged
Biochemistry
Genetics and Molecular Biology(all)

Cancer
Immunotherapy
Middle Aged
immune checkpoint blockade
medicine.disease
Peripheral blood
Coculture Techniques
030104 developmental biology
medicine.anatomical_structure
Cancer research
Leukocytes
Mononuclear

microsatellite instable
Female
immunotherapy
Colorectal Neoplasms
Genetics and Molecular Biology(all)
Zdroj: 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, Monkhorst, K, Haanen, J, Clevers, H, Schumacher, T N & Voest, E E 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
Cell, 174(6), 1586-1598.e12. Cell Press
Cell, 174(6), 1586-1598.e12. Elsevier B.V.
Cell
Cell, 174(6), 1586. Cell Press
ISSN: 0092-8674
Popis: 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. A modified patient-derived tumor organoids system allows the expansion of tumor-specific T cells from blood for personalized analysis of their anti-cancer properties.
Databáze: OpenAIRE