TNF and cancer: For example, in PDAC patients the production of indoleamine-2,3-dioxygenase (IDO) and MMP-9 from cancer cells can significantly limit the cytotoxicity of NK cells, inducing anergic/hypofunctional NK cells in vitro through decreasing the expression of NKp30, NKG2D, and perforin, as well as inhibiting the secretion of IFN-γ and tumor necrosis factor (TNF-α) [63,69].