KLRK1 and neoplasm: IL-21, produced by activated CD4+ T cells, which by its own activates both CD8+ T cells and NK cells promoting NKG2D-dependent killing of tumor cells (Takaki et al., 2005), when secreted in combination with IL-2 induces downregulation of NKG2D, thus silencing of the receptor-mediated immunosurveillance (Burgess et al., 2006).