Figure 2.

Inhibition of NK cell cytotoxicity by other immune cells. Immune suppressive cell types in the TME interact directly with NK cells to inhibit their function through both contact-dependent and contact-independent downregulation of NK cell activating receptors, typically mediated by TGF-β. TAMs promote the maintenance of membrane-bound CD16, which reduces NK activation. NK cell function can also be modulated indirectly through multiple interactions between these different cell types. Cytokine secretion by MDSCs promote the expansion of Tregs, which apart from directly inhibiting NK cell functions, also limits the availability of IL-2 from CD4+ T cells, thus preventing NK cell stimulation. Platelets in the TME also interact with tumour cells directly, shielding them from NK cell recognition and killing; cleaving activating ligands on the tumour cell surface; and equipping tumour cells with MHC Class I molecules to facilitate immune evasion.