Figure 1. Restoring intratumoral NK cell functions with cytokines.

When tumor cells lose MHC class I expression, which can occur for a variety of reasons, they disarm the function of NK cells, which become “unlicensed.” However, upon administration of the combination of IL-12 plus IL-18 or H9, NK cells regain their functions, including phosphorylation of the stress kinase ERK1/2, production of granzyme B, and secretion of IFN-γ, and recover their capacity to control tumor progression.