Furthermore, as the contribution of several other factors in addition to inhibitory receptors leads to an immune escape of NK cells, for example, downregulation of activating receptors, molecular checkpoints of the activation pathways such as Cbl, GSK-3β, DGKζ, and CIS, and tumor environment suppressors, a combination of strategies countering each of these processes could lead to a more complementary and synergistic potent immune response (369). This evidence concerns the gene CISH and neoplasm.