Lenalidomide down regulates the production of interferon-γ and the expression of inhibitory cytotoxic receptors of human Natural Killer cells

Lenalidomide, a daughter molecule of Thalidomide, and IMIDs® are immunomodulatory drugs that have been described as having immunomodulatory properties and anti-tumor activity. The effect of Lenalidomide towards Peripheral Blood Mononuclear Cells (PBMC) has been studied and direct effects towards T cells have been described, such as an increase of interferon-γ (IFN-γ) and interleukin (IL)-2 production. As a consequence, it has been also described that IL-2 subsequently activates Natural Killer (NK) cells. Nevertheless, direct effects of Lenalidomide on NK cells from healthy volunteers have never been described, if searched. Here we show that Lenalidomide can inhibit the production of IFN-γ by NK cells from healthy donors. It also modifies the phenotype of NK cells through a decrease of the expression of Killer cell Immunoglobulin-like Receptors (KIRs) and NKp46. However, we did not detect consequence of these phenotype modifications on the cytotoxic potential of NK cells.