Downregulation of NKG2DLs by TGF-β in human lung cancer cells

BackgroundTransforming growth factor beta (TGF-beta) is a typical immuno-inhibitory cytokine and highly secreted by lung cancer cells. It was supposed that its immunosuppressive effects to NK cell might be related with the altered expression of activating and inhibitory molecules in lung cancer cells. In this study, we examined the expression of NKG2DLs, PD-L1 and PD-L2 in lung cancer cells after treatment of TGF-beta and a TGF-beta inhibitor, Galunisertib (LY2157299).ResultsTGF-beta reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-beta on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-beta, it was thought that TGF-beta induced the expression of MMP2 which facilitated the shedding of the NKG2DLs in cancer cells. However, the expression of PD-L1, L2 were not changed by treatment with TGF-beta or Galunisertib.ConclusionsTherefore, inhibition of TGF-beta might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.

Automated summary

In this study, it was found that TGF-beta reduced the surface protein levels of five NKG2DLs in lung cancer cells without altering transcription levels. Galunisertib reversed this effect of TGF-beta on NKG2DLs expression.