The role of interleukin 15 in neoplasia

Interleukin 15 is a pleiotropic cytokine of the four α helix bundle family. Binding to a heterotrimeric receptor complex, which consists of a unique, high affinity IL-15Rα-chain and IL-2/IL-15Rβ and IL-2Rγ chains, IL-15 activates signaling pathways leading to activation and proliferation of T and B cells, as well as natural killer cells. At the same time, IL-15 protects effector cells from T regulatory cells and does not induce immune tolerance. The significant regulatory action of IL-15 on the immune system provides new opportunities for development of anti-cancer therapies.As documented in many experiments using different tumor models, IL-15 enhances antitumor effects. To improve the efficiency of IL-15, several strategies, including combination with other anti-cancer therapies such as chemotherapy, additional use of antibodies (anti-PD-L1, anti-CTLA-4, anti-CD40), or other cytokines, have been evaluated. Increased anti-tumor activity can also be obtained by using IL-15 agonists.However, acting as a growth factor for immune cells but also for tumor cells, IL-15 may promote their proliferation, survival and dissemination. Of significance seems the role of IL-15 in the pathogenesis of hematological malignancies, which is due to the involvement in the proliferation and differentiation of NK, T and B cells.Currently, several experimental strategies are available to block biological activity of IL-15. Among compounds inhibiting the activity of IL-15 are not only monoclonal antibodies interacting directly with the cytokine or with IL-15R subunits, but also mutant forms of IL-15 and protein constructs