Oncotarget

Research Papers:

TUSC2 downregulates PD-L1 expression in non-small cell lung cancer (NSCLC)

Xiaobo Cao, Yang Zhao, Jing Wang, Bingbing Dai, Emanuela Gentile, Jing Lin, Xingxiang Pu, Lin Ji, Shuhong Wu, Ismail Meraz, Mourad Majidi and Jack A. Roth _

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Oncotarget. 2017; 8:107621-107629. https://doi.org/10.18632/oncotarget.22581

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Abstract

Xiaobo Cao1, Yang Zhao2, Jing Wang2, Bingbing Dai3, Emanuela Gentile1, Jing Lin1, Xingxiang Pu4, Lin Ji1, Shuhong Wu1, Ismail Meraz1, Mourad Majidi1 and Jack A. Roth1

1Department of Thoracic and Cardiovascular Surgery, Section of Thoracic Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

2Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

3Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

4Department of Thoracic Medical Oncology, Hunan Cancer Hospital, Changsha, China

Correspondence to:

Jack A. Roth, email: jroth@mdanderson.org

Keywords: PD-L1; TUSC2; mTOR; protein translation; lung cancer

Received: September 20, 2017     Accepted: November 01, 2017     Published: November 21, 2017

ABSTRACT

Expression of the TUSC2 tumor-suppressor gene in TUSC2-deficient NSCLC cells decreased PD-L1 expression and inhibited mTOR activity. Overexpressing TUSC2 or treatment with rapamycin resulted in similar inhibition of PD-L1 expression. Both TUSC2 and rapamycin decreased p70 and SK6 phosphorylation, suggesting that TUSC2 and rapamycin share the same mTOR target. Microarray mRNA expression analysis using TUSC2-inducible H1299 showed that genes that negatively regulate the mTOR pathway were significantly upregulated by TUSC2 compared with control. The presence of IFN-γ significantly increased PD-L1 expression in lung cancer cell lines, but overexpressing TUSC2 in these cell lines prevented PD-L1 from increasing in the presence of IFN-γ. Taken together, these findings show that TUSC2 can decrease PD-L1 expression in lung cancer cells. This ability to modify the tumor microenvironment suggests that TUSC2 could be added to checkpoint inhibitors to improve the treatment of lung cancer.


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