title: Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer.
abstract: OBJECTIVE
  The negative regulatory programmed death-1/programmed death-1 ligand (PD-1/PD-L) pathway in T-cell activation has been suggested to play an important role in tumor evasion from host immunity. In this study, we investigated the expression of PD-L1 and PD-L2 in human esophageal cancer to define their clinical significance in patients' prognosis after surgery.
  
  
  METHODS
  PD-L1 and PD-L2 gene expression was evaluated in 41 esophagectomy patients by real-time quantitative PCR. The protein expression was also evaluated with newly generated monoclonal antibodies that recognize human PD-L1 (MIH1) and PD-L2 (MIH18).
  
  
  RESULTS
  The protein and the mRNA levels of determination by immunohistochemistry and real-time quantitative PCR were closely correlated. PD-L-positive patients had a significantly poorer prognosis than the negative patients. This was more pronounced in the advanced stage of tumor than in the early stage. Furthermore, multivariate analysis indicated that PD-L status was an independent prognostic factor. Although there was no significant correlation between PD-L1 expression and tumor-infiltrating T lymphocytes, PD-L2 expression was inversely correlated with tumor-infiltrating CD8(+) T cells.
  
  
  CONCLUSIONS
  These data suggest that PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer and provide the rationale for developing novel immunotherapy of targeting PD-1/PD-L pathway.
authors.affiliation: Department of Surgery, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohigashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.forename: Yukishige
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tsurui
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hamada
authors.forename: Naoya
authors.initials: N
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Mizuno
authors.forename: Ryo
authors.initials: R
authors.lastname: Yoriki
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kashizuka
authors.forename: Katsunari
authors.initials: K
authors.lastname: Yane
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Tsushima
authors.forename: Noriko
authors.initials: N
authors.lastname: Otsuki
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000368:Aged; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000032:analysis / Q000235:genetics*; D060890:B7-H1 Antigen; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D010455:Peptides / Q000032:analysis / Q000235:genetics*; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C556977:PDCD1LG2 protein, human; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger