In this review, to explore the interrelationship between exosome recruitment and metalloprotease cleavage, we will discuss, as a model, the regulation of the release of NKG2D-ligands, proteins whose expression is induced by stress and signals for immune activation, but that can also act as decoys reducing the intensity of the immune response when they are secreted from tumor cells. Here, KLRK1 is linked to neoplasm.