Journal article
Synergistic targeting of breast cancer stem-like cells by human 3 T cells and CD8 T cells
HC Chen, N Joalland, JS Bridgeman, FS Alchami, U Jarry, MWA Khan, L Piggott, Y Shanneik, J Li, MJ Herold, T Herrmann, DA Price, AM Gallimore, RW Clarkson, E Scotet, B Moser, M Eberl
Immunology and Cell Biology | WILEY | Published : 2017
DOI: 10.1038/icb.2017.21
Abstract
The inherent resistance of cancer stem cells (CSCs) to existing therapies has largely hampered the development of effective treatments for advanced malignancy. To help develop novel immunotherapy approaches that efficiently target CSCs, an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC-restricted 3 T cells and antigen-specific CD8 + T cells. Stable lines with characteristics of breast CSC-like cells were generated from ras-transformed human mammary epithelial (HMLER) cells as confirmed by their CD44 hi CD24 lo GD2 + phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non-adh..
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Awarded by Medical Research Council
Funding Acknowledgements
We would like to thank Robert Weinberg for providing HLMER cells; James Riley and Mai Ping Tan for plasmids; Andrew Thomas for recombinant FluM1 protein and HLA-A2 tetramers; Fariba Navid for hu14.18K322A antibodies; Daniel Olive for BTN3A blocking antibodies; Hassan Jomaa for synthetic HMB-PP; Nooshin Tabatabaei-Zavareh for custom-made gamma delta T-cell isolation kits; Catherine Naseriyan, Kelly Miners and Kristin Ladell for cell sorting; Aled Clayton for help with confocal microscopy; Tamsin Dockree, Chia-Te Liao and Lisa Starick for help with lentiviral constructs; Emily Colbeck, Emma Jones and Anwen Williams for help with histology; Garry Dolton, Ellyn Hughes and Emma Kempshall for help with animal studies; and the Cellular and Tissular Imaging Core Facility of Nantes University (MicroPICell) and Lola Boutin for help with video microscopy and calcium experiments. This research was supported by the Wales Cancer Research Centre and the Cardiff CR-UK Centre Development Fund; Cancer Research UK grants C28524/A9497, C42921/A13823 and C16731/A21200; Institut National de la Sante et de la Recherche Medicale (INSERM); Centre National de la Recherche Scientifique (CNRS); Universite de Nantes; Institut National du Cancer (INCa PLBIO 2014-155) and Investissements d'Avenir (Agence Nationale de la Recherche-Programme Laboratoires d'Excellence Immunotherapy Graft Oncology; #ANR 11 LABX-0016-01); Wilhelm Sander-Stiftung grant 2013.907.1; Tenovus PhD Studentships to H-CC and LP; a Government Scholarship for Study Abroad from the Taiwanese Ministry of Education (H-CC); an Erasmus+ Traineeship (YS); and a Cardiff Incoming Visiting Fellowship (TH). DAP is supported by a Wellcome Trust Senior Investigator Award (100326/Z/12/Z).