Interleukin-15: New kid on the block for antitumor combination therapy

Interleukin (IL)-15 is one of the most promising molecules to be used in antitumor immune therapy, as it is able to stimulate the main killer cells of both the innate and adaptive immune system. Although this cytokine can be used as a stand-alone immunotherapeutic agent, IL-15 will probably be most efficient in combination with other strategies to overcome high tumor burden, immune suppression of the tumor microenvironment and/or the short half-life of IL-15. In this review, we will discuss the combination strategies with IL-15 that have been tested to date in different animal tumor models, which include chemotherapy, other immunostimulatory cytokines, targeted therapy, adoptive cell transfer and gene therapy. In addition, we give an overview of IL-15 combination therapies that are currently tested in clinical studies to treat patients with hematological or advanced solid tumors.