*2.2.3.4 Conclusions/future directions*

In order to effectively achieve immune surveillance, immunosuppressive signals within the tumor microenvironment must be interrupted. The PD-1/PD-L1 signaling blockade was developed in accordance with this principle. Tumors have been shown to secrete cytokines associated with suppression of T-cells and NK cells, and past murine studies have shown circulating IL-18 in low levels originating from tumor cells can suppress NK anti-tumor activity [41]. The principles of checkpoint blockade can be applied here with the development of a neutralizing antibody to IL-18, suggesting the potential of checkpoint inhibition to improve in vivo NK cell activity.
