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BMC Immunology

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Open Access 01-12-2021 | Lung Cancer | Research

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

Authors: Young Shin Lee, Hojung Choi, Hae-Ryung Cho, Woo-Chang Son, You-Soo Park, Chi-Dug Kang, Jaeho Bae

Published in: BMC Immunology | Issue 1/2021

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.

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Title: Downregulation of NKG2DLs by TGF-β in human lung cancer cells
Authors: Young Shin Lee
Hojung Choi
Hae-Ryung Cho
Woo-Chang Son
You-Soo Park
Chi-Dug Kang
Jaeho Bae
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Lung Cancer
Lung Cancer
Lung Cancer
Published in: BMC Immunology / Issue 1/2021
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/s12865-021-00434-8

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