In this sense, the EMT-inducing cytokines TGFβ, IL-10, IL-6, produced by tumor cells or by immunosuppressive cells in TME, can either directly downmodulate expression of activating NK cell receptors (NKG2D, NCRs, DNAM1, CD16) or indirectly by inducing the differentiation of suppressive immune cells such as M2 macrophages, tolerogenic DCs, Tregs and MDSCs and their ability to produce additional immunosuppressive factors (Stojanovic et al., 2013; Konjević et al., 2016, 2017a, 2019). This evidence concerns the gene CD226 and neoplasm.