Local IL-15-immunotherapy to treat melanoma

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.