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 |
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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 |
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