title: Expression of PD-L1 and HLA Class I in Esophageal Squamous Cell Carcinoma: Prognostic Factors for Patient Outcome.
abstract: BACKGROUND
  Programmed cell death 1 ligand 1 (PD-L1) and human leukocyte antigen (HLA) class I molecules on malignant cell surfaces are pivotal for tumor immunity. The clinical significance of their expression in patients with esophageal squamous cell carcinoma (ESCC) remains to be determined.
  
  
  METHODS
  PD-L1 and HLA class I protein expression was investigated by immunohistochemical staining of resected specimens from 90 ESCC patients who underwent radical surgery without preoperative therapy. The relationships between the expression of PD-L1 and HLA class I and clinicopathologic factors and patient prognosis were assessed.
  
  
  RESULTS
  High expression of PD-L1 and HLA class I were observed in 17 (18.9 %) and 35 (38.9 %) of 90 cases, respectively. High PD-L1 expression was correlated with the depth of tumor invasion (P = 0.0379), lymph node metastasis (P = 0.0031), recurrence (P = 0.0085), and poor overall survival (OS) (5-year survival rate; low/high: 60.9/28.4 %, P = 0.0110). Among those patients with high expression of HLA class I, high PD-L1 expression was correlated with significantly poorer recurrence-free survival (median survival time, low/high: 102.5/3.1 months, P = 0.0016) and poorer OS (median survival time, low/high: 102.5/13.1 months, P = 0.0027). Multivariate analysis showed that combined high PD-L1/high HLA class I expression was an independent prognostic factor for recurrence-free survival (hazard ratio 2.88, 95 % confidence interval 1.02-7.04, P = 0.0455) and OS (hazard ratio 2.95, 95 % confidence interval 1.03-7.50, P = 0.0447).
  
  
  CONCLUSIONS
  High PD-L1 expression was a significant independent prognostic factor in ESCC patients with high HLA class I expression.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. sito@med.kyushu-u.ac.jp.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Okano
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsutsumi
authors.affiliation: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.|Translational Research Laboratory, Taiho Pharmaceutical Co. Ltd., Tokushima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsukihara
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kippei
authors.initials: K
authors.lastname: Ohgaki
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.affiliation: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.|Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara