dc.contributor.author | Hanes, Mark | |
dc.date.accessioned | 2017-12-15T12:54:09Z | |
dc.date.available | 2017-12-15T12:54:09Z | |
dc.date.issued | 2017-12-15T12:54:09Z | |
dc.identifier.uri | http://hdl.handle.net/10222/73526 | |
dc.description.abstract | Intratumoural (i.t.) IL-2 is an effective treatment for cutaneous, metastatic melanoma. However, treating patients with high metastatic burden can be very challenging. Another common γ chain cytokine, IL-15, facilitates the expansion and maintenance of antigen (Ag)-experienced CD8+ T cells and endows naïve CD8+ T cells with cytotoxic capability and surface molecules that enhance their ability to traffic to secondary lymphoid organs (SLOs) for primary immune activation. We asked whether i.t. IL-15 might increase antitumour immunity by increasing Ag-specific CD8+ T cell numbers. To test this, we used the murine bilateral B16F10 melanoma model, high-dimensional single cell immune profiling, and in vitro co-culture assays. We show that i.t. IL-15 is equal to if not better than IL-2 at controlling the growth of treated B16F10 lesions; and that IL-15 has notable regulatory effects on distant non-treated tumours; orchestrates an influx of Ag-experienced CD8+ T cells to treated tumours and SLOs; enhances the functional quality/reactivity of systemic CD8+ T cells; while beneficially having limited influence on regulatory T cell numbers. | en_US |
dc.language.iso | en | en_US |
dc.subject | Immunotherapy | en_US |
dc.subject | Cancer | en_US |
dc.subject | Melanoma | |
dc.title | Local IL-15-immunotherapy to treat melanoma | en_US |
dc.date.defence | 2017-08-24 | |
dc.contributor.department | Department of Pathology | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | Dr. Andrew Stadnyk | en_US |
dc.contributor.graduate-coordinator | Dr. Wenda Greer | en_US |
dc.contributor.thesis-reader | Dr. Paola Marcato | en_US |
dc.contributor.thesis-reader | Dr. Shashi Gujar | en_US |
dc.contributor.thesis-reader | Dr. David Waisman | en_US |
dc.contributor.thesis-supervisor | Dr. Carman Giacomantonio | en_US |
dc.contributor.ethics-approval | Received | en_US |
dc.contributor.manuscripts | Not Applicable | en_US |
dc.contributor.copyright-release | Not Applicable | en_US |