Oncotarget

Research Papers:

The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression

Miao-Fen Chen, Ping-Tsung Chen, Wen-Cheng Chen, Ming-Shian Lu, Paul-Yang Lin and Kuan-Der Lee _

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Oncotarget. 2016; 7:7913-7924. https://doi.org/10.18632/oncotarget.6861

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Abstract

Miao-Fen Chen1,2, Ping-Tsung Chen2,3, Wen-Cheng Chen1,2, Ming-Shian Lu4, Paul-Yang Lin5, Kuan-Der Lee2,3

1Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan

2College of Medicine, Chang Gung University, Chiayi, Taiwan

3Department of Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan

4Department of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan

5Department of Pathology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan

Correspondence to:

Kuan-Der Lee, e-mail: leecgmh@gmail.com

Keywords: PD-L1, esophageal SCC, IL-6, CD8+ T cell

Received: September 30, 2015    Accepted: January 02, 2016    Published: January 09, 2016

ABSTRACT

The aim of this study was to assess the significance of programmed cell death 1 ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) and its association with IL-6 and radiation response. Weretrospectively enrolled 162 patients with ESCC, and examined the correlation between PD-L1 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T and TE2 were selected for cellular experiments to investigate the role of PD-L1 in T cell functions and radiation response. Here we demonstrated that PD-L1 expression was significantly higher in esophageal cancer specimens than in non-malignant epithelium. In clinical outcome analysis, this staining of PD-L1 was positively linked to the clinical T4 stage (p=0.004), development of LN metastasis (p=0.012) and higher loco-regional failure rate (p=0.0001). In addition, the frequency of PD-L1 immunoreactivity was significantly higher in IL-6-positive esophageal cancer specimens. When IL-6 signaling was inhibited in vitro, the level of PD-L1 is significantly down-regulated. PD-L1 is a significant predictor for poor treatment response and shorter survival.As demonstrated through in vitro experiments, Irradiation increased PD-L1 expression in human esophageal cancer cells. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells might be the mechanisms responsible to the role of PD-L1 in radiation response. In conclusion, PD-L1 is important in determining the radiation response and could predict the prognosis of patients with esophageal SCC. Therefore, we suggest inhibition of PD-L1 as a potential strategy for the treatment of esophageal SCC.


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