Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer

Cancer Lett. 2008 Sep 8;268(1):98-109. doi: 10.1016/j.canlet.2008.03.056. Epub 2008 May 16.


We investigated the expression pattern and clinical significance of the costimulatory ligands B7-1, B7-2, B7-H1, and B7-DC, and their counter-receptors CTLA-4 and PD-1 in pancreatic cancer. Gene expression of all examined costimulatory molecules was significantly upregulated in pancreatic cancer tissues. B7-1, B7-2, B7-H1, and B7-DC protein was detectable in pancreatic cancer cells. Only the expression of B7-H1 significantly correlated with postoperative survival (p<0.0001). B7-H1 was inducible in cultured pancreatic cancer cells by IFN-gamma and significantly correlated with the level of IFN-gamma expression in human pancreatic cancer tissues (Spearman rho=0.4536,p=0.0029). B7-H1 positive tumors showed an increased prevalence of tumor-infiltrating regulatory T cells (Tregs) compared to B7-H1 negative tumors. Among the investigated costimulatory molecules only tumor-associated B7-H1 seems to be of prognostic relevance in pancreatic cancer. B7-H1 might, therefore, be involved in the downregulation of antitumor responses through regulation of Tregs in pancreatic cancer. Our findings also suggest a dual role of IFN-gamma in antitumor response. Through induction of B7-H1 in pancreatic cancer cells IFN-gamma might contribute to the evasion of antitumor immunity.

MeSH terms

  • Antigens, CD / metabolism
  • B7-1 Antigen / metabolism*
  • B7-2 Antigen / metabolism
  • CTLA-4 Antigen
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Humans
  • Interferon-gamma / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Programmed Cell Death 1 Ligand 2 Protein
  • Survival Analysis
  • T-Lymphocytes, Regulatory / immunology
  • Up-Regulation


  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Interferon-gamma