Interleukin-15 biology and its therapeutic implications in cancer

Cancer immunotherapy is designed to stimulate the immune system to reject and destroy tumors. Recently, interleukin-15 (IL-15), a member of the four alpha-helix bundle family of cytokines, has emerged as a candidate immunomodulator for the treatment of cancer. IL-15 acts through its specific receptor, IL-15R alpha, which is expressed on antigen-presenting dendritic cells, monocytes and macrophages. IL-15 exhibits broad activity and induces the differentiation and proliferation of T, B and natural killer (NK) cells. It also enhances the cytolytic activity of CD8(+) T cells and induces long-lasting antigen-experienced CD8(+)CD44(hi) memory T cells. IL-15 stimulates differentiation and immunoglobulin synthesis by B cells and induces maturation of dendritic cells. It does not stimulate immunosuppressive T regulatory cells (Tregs). Thus, boosting IL-15 activity could enhance innate and specific immunity and fight tumors. Here we review aspects of IL-15 biology that make it a promising agent for anticancer therapy. We also discuss preclinical models in which IL-15 has demonstrated antitumor activity and highlight ongoing clinical trials of IL-15 in patients with cancer and HIV infection.