The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression
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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
Kuan-Der Lee, e-mail: [email protected]
Keywords: PD-L1, esophageal SCC, IL-6, CD8+ T cell
Received: September 30, 2015 Accepted: January 02, 2016 Published: January 09, 2016
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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