title: The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression.
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.
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan.|College of Medicine, Chang Gung University, Chiayi, Taiwan.
authors.forename: Miao-Fen
authors.initials: MF
authors.lastname: Chen
authors.affiliation: College of Medicine, Chang Gung University, Chiayi, Taiwan.|Department of Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan.
authors.forename: Ping-Tsung
authors.initials: PT
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan.|College of Medicine, Chang Gung University, Chiayi, Taiwan.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Department of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan.
authors.forename: Ming-Shian
authors.initials: MS
authors.lastname: Lu
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan.
authors.forename: Paul-Yang
authors.initials: PY
authors.lastname: Lin
authors.affiliation: College of Medicine, Chang Gung University, Chiayi, Taiwan.|Department of Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan.
authors.forename: Kuan Der
authors.initials: KD
authors.lastname: Lee
mesh_terms: D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000556:secondary / Q000628:therapy; D059248:Chemoradiotherapy; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000097:blood*; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D015850:Interleukin-6
keywords: CD8+ T cell; IL-6; PD-L1; esophageal SCC