Nevertheless, because the activating receptor NKG2D/NKG2DL pathway is of major importance for NK activation, cytolytic functions and cytokine secretion, the observed CAFs and MMPs-dependent decrease in MICA/B expression at the surface of melanoma tumor cells leads to a strong alteration of the NK cells cytotoxic activity against their melanoma target cells, as well as a diminished secretion of IFN-γ by NK cells following recognition of their targets. The gene discussed is KLRK1; the disease is melanoma.