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// Miao-Fen Chen 1, 2 , Ping-Tsung Chen 2, 3 , Wen-Cheng Chen 1, 2 , Ming-Shian Lu 4 , Paul-Yang Lin 5 , Kuan-Der Lee 2, 3 1 Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan 2 College of Medicine, Chang Gung University, Chiayi, Taiwan 3 Department of Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan 4 Department of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan 5 Department 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.
Chen et al. (Sat,) studied this question.