Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer

Clin Cancer Res. 2005 Apr 15;11(8):2947-53. doi: 10.1158/1078-0432.CCR-04-1469.


Purpose: 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.

Experimental design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD
  • B7-1 Antigen / analysis
  • B7-1 Antigen / genetics*
  • B7-H1 Antigen
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophagus / metabolism
  • Esophagus / pathology
  • Esophagus / surgery
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Peptides / analysis
  • Peptides / genetics*
  • Prognosis
  • Programmed Cell Death 1 Ligand 2 Protein
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Analysis


  • Antigens, CD
  • B7-1 Antigen
  • B7-H1 Antigen
  • CD274 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • PDCD1LG2 protein, human
  • Peptides
  • Programmed Cell Death 1 Ligand 2 Protein
  • RNA, Messenger