Figure 1. Bolstering cancer immunotherapy with IL-15. (I) IL-15 is an immunostimulatory cytokine that typically is found pre-bound to the IL-15 receptor a-chain (IL-15RA) on antigen-presenting cells (APCs) such as dendritic cells. These APCs display IL-15 to a heterodimeric receptor complex on T and NK cells to induce their proliferation.

The receptor complex is composed of the IL-2 receptor b-chain (CD122; IL2RB) and IL-2 receptor g-chain (CD132; IL2RG). IL-15 also inhibits apoptosis pathways in the various leukocyte populations, resulting in more persistent immune cells.

Candidate therapies that stimulate IL-15 activity can potentially bolster the efficacy of cancer immunotherapies.

One potential combination is with checkpoint inhibitors such as the anti-programmed cell death 1 (PDCD1; PD-1; CD279) mAbs, which block the interaction between PD-1 and programmed cell death 1 ligand 1 (CD274 molecule; PD-L1; B7-H1). The combination could yield a larger and more persistent pool of immune cells available to attack cancer cells and thus could result in a more robust antitumor response.

(II) Without IL-15 stimulation, fewer immune cells are around to attack cancer cells after treatment with a checkpoint inhibitor.