Biological effects of IL-15 on immune cells and its potential for the treatment of cancer

Interleukin-15 (IL-15) has recently emerged as a novel immunomodulatory cytokine in cancer immunotherapy. IL-15 has the potential to reject and destroy cancer cells in the tumor microenvironment by expanding and activating natural killer (NK), natural killer T (NKT), and memory (m) CD8+T cells. Due to the feasible outcomes obtained from preclinical studies and phase 1/2 clinical trials, IL-15-based therapy, including chimeric antigen receptor (CAR) T cell or CAR NK cell infusion following in vitro expansion in the presence of IL-15, used in combination with checkpoint inhibitors and other therapy may extend to clinical practice in the future. It is also important to understand the biological characteristics of IL-15 to ensure the maximal benefit of therapeutic strategies. Here, we summarize the current development of IL-15 in the following areas: anti-tumor mechanisms in the tumor microenvironment, advances in IL-15-based therapy itself or in combination with other methods, including biological agents, monoclonal antibodies, and adoptive immunotherapy.