Young Shin Lee1, Hojung Choi1, Hae-Ryung Cho1,2, Woo-Chang Son3, You-Soo Park3, Chi-Dug Kang1, Jaeho Bae4,5. 1. Department of Biochemistry, Pusan National University School of Medicine, Yangsan, 50162, South Korea. 2. PNU BK21 Plus Biomedical Science Education Center, Pusan National University School of Medicine, Yangsan, 50612, South Korea. 3. Department of Research Center, Dongnam Institute of Radiological and Medical Sciences, Gijang, Busan, 46033, South Korea. 4. Department of Biochemistry, Pusan National University School of Medicine, Yangsan, 50162, South Korea. biosole@pusan.ac.kr. 5. PNU BK21 Plus Biomedical Science Education Center, Pusan National University School of Medicine, Yangsan, 50612, South Korea. biosole@pusan.ac.kr.
Abstract
BACKGROUND: Transforming growth factor beta (TGF-β) 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-β and a TGF-β inhibitor, Galunisertib (LY2157299). RESULTS: TGF-β reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-β on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-β, it was thought that TGF-β 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-β or Galunisertib. CONCLUSIONS: Therefore, inhibition of TGF-β might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.
BACKGROUND: Transforming growth factor beta (TGF-β) 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-β and a TGF-β inhibitor, Galunisertib (LY2157299). RESULTS: TGF-β reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-β on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-β, it was thought that TGF-β 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-β or Galunisertib. CONCLUSIONS: Therefore, inhibition of TGF-β might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.
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