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dc.contributor.authorChen, H-C
dc.contributor.authorJoalland, N
dc.contributor.authorBridgeman, JS
dc.contributor.authorAlchami, FS
dc.contributor.authorJarry, U
dc.contributor.authorKhan, MWA
dc.contributor.authorPiggott, L
dc.contributor.authorShanneik, Y
dc.contributor.authorLi, J
dc.contributor.authorHerold, MJ
dc.contributor.authorHerrmann, T
dc.contributor.authorPrice, DA
dc.contributor.authorGallimore, AM
dc.contributor.authorClarkson, RW
dc.contributor.authorScotet, E
dc.contributor.authorMoser, B
dc.contributor.authorEberl, M
dc.date.accessioned2021-02-03T23:58:38Z
dc.date.available2021-02-03T23:58:38Z
dc.date.issued2017-08-01
dc.identifierpii: icb201721
dc.identifier.citationChen, H. -C., Joalland, N., Bridgeman, J. S., Alchami, F. S., Jarry, U., Khan, M. W. A., Piggott, L., Shanneik, Y., Li, J., Herold, M. J., Herrmann, T., Price, D. A., Gallimore, A. M., Clarkson, R. W., Scotet, E., Moser, B. & Eberl, M. (2017). Synergistic targeting of breast cancer stem-like cells by human gamma delta T cells and CD8(+) T cells. IMMUNOLOGY AND CELL BIOLOGY, 95 (7), pp.620-629. https://doi.org/10.1038/icb.2017.21.
dc.identifier.issn0818-9641
dc.identifier.urihttp://hdl.handle.net/11343/259007
dc.description.abstractThe 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 γδ 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 CD44hi CD24lo GD2+ phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non-adherent conditions, as well as their potent tumorigenicity, self-renewal and differentiation in xenografted mice. The resistance of CSC-like cells to γδ T cells could be overcome by inhibition of farnesyl pyrophosphate synthase (FPPS) through pretreatment with zoledronate or with FPPS-targeting short hairpin RNA. γδ T cells induced upregulation of MHC class I and CD54/ICAM-1 on CSC-like cells and thereby increased the susceptibility to antigen-specific killing by CD8+ T cells. Alternatively, γδ T-cell responses could be specifically directed against CSC-like cells using the humanised anti-GD2 monoclonal antibody hu14.18K322A. Our findings identify a powerful synergism between MHC-restricted and non-MHC-restricted T cells in the eradication of cancer cells including breast CSCs. Our research suggests that novel immunotherapies may benefit from a two-pronged approach combining γδ T-cell and CD8+ T-cell targeting strategies that triggers effective innate-like and tumour-specific adaptive responses.
dc.languageEnglish
dc.publisherWILEY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleSynergistic targeting of breast cancer stem-like cells by human gamma delta T cells and CD8(+) T cells
dc.typeJournal Article
dc.identifier.doi10.1038/icb.2017.21
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleImmunology and Cell Biology
melbourne.source.volume95
melbourne.source.issue7
melbourne.source.pages620-629
dc.rights.licenseCC BY
melbourne.elementsid1197110
melbourne.contributor.authorHerold, Marco
dc.identifier.eissn1440-1711
melbourne.accessrightsOpen Access


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