Figure 1.

Protocols to recover/improve NK function. We describe several mechanisms to improve NK activity in patients. Naïve NK cells can be “armed” with mAbs that recognize tumor antigens (Ags) to improve their cytolytic activity against cancer cells (6). If specific mAbs against Ags of different pathogens are available, they can be used to arm NK cells to fight infections, mainly in immune compromised patients (54, 55). NK cells can be expanded (eNK) to recover NK cell functions in several diseases such as cancer, autoimmune diseases and infections (32). Treatment of patients with metabolic drugs that modify the microenvironment of the target can increase the function of both “armed” NK and eNK (25, 53). We also believe that it is possible transfer specific NK cell subsets to treat different diseases such as cancers (11–13), including glioblastoma (56) that has a poor prognosis. Some NK subsets, e.x. memory NK cells could also fight infections (57) when engrafted in patients. Finally, in autoimmune diseases could be clinically relevant to replace immature CD56^bright NK, which are mostly proinflammatory with mature CD56^dim NK, which eliminate activated immune cells. These two NK subsets differentially express various chemokine receptors, which attract them to distinct organs (58, 59). Hence, locally playing with different chemokines should naturally facilitating the recruitment of a specific subset.