High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells
Authors Chen X, Zhang Q, Luo Y, Gao C, Zhuang X, Xu G, Qaio T
Received 6 July 2016
Accepted for publication 5 September 2016
Published 21 October 2016 Volume 2016:9 Pages 6511—6518
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 2
Editor who approved publication: Dr Ingrid Espinoza
Xue Chen,1 Qi Zhang,1 Youjun Luo,1 Caixia Gao,1 Xibing Zhuang,1 Guoxiong Xu,2 Tiankui Qiao1
1Department of Oncology, Jinshan Hospital, Medical Center of Fudan University, 2Department of Center laboratory, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China
Objectives: Irradiation resistance appears as local recurrence and distant metastasis in advanced stages of non-small cell lung cancer (NSCLC). High-dose irradiation combined with immunotherapy improved overall survival and local control of NSCLC. This study explored the underlying molecular mechanism by which the effect of high-dose irradiation plus toll-like receptor 9 (TLR9) agonist CpG oligodeoxynucleotide (CpG ODN) 7909 on NSCLC.
Materials and methods: NSCLC H460 cells were exposed to constant high-dose irradiation (6.37 Gy) in irradiation (IR) group and the irradiation plus CpG group. Gene expression was assessed using quantitative reverse transcriptase-polymerase chain reaction and Western blot. Knockdown of nuclear factor kappa B (NF-κB) p65 expression was conducted using p65 siRNA.
Results: Expression of programmed death-ligand 1 (PD-L1) mRNA was significantly decreased in IR combined with CpG ODN 7909 group compared with the control or IR-alone groups (P<0.05). TLR9 expression was also obviously increased in the combination group compared with the control (P<0.05). Moreover, expression of NF-κB p65 was apparently reduced in the combination group compared with the control (P<0.05). However, expression of PD-L1 was significantly decreased after knockdown of p65 in IR group (P<0.05), but increased in the combination group (P<0.05) and slightly increased in CpG ODN-alone group (P<0.05), which was opposite to that without p65 knockdown group.
Conclusion: This study demonstrated that radiotherapy combined with CpG ODN 7909 was able to downregulate PD-L1 expression through inhibition via the NF-κB signaling pathway.
Keywords: CpG ODN, irradiation, immune escape, NF-κB, non-small cell lung cancer, PD-L1
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