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

Martin Loos, Nathalia A. Giese, Jörg Kleeff, Thomas Giese, Matthias M. Gaida, Frank Bergmann, Melanie Laschinger, Markus W.Büchler, Helmut Friess

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

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-γ and significantly correlated with the level of IFN-γ expression in human pancreatic cancer tissues (Spearman ρ = 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-γ in antitumor response. Through induction of B7-H1 in pancreatic cancer cells IFN-γ might contribute to the evasion of antitumor immunity.

Original languageEnglish
Pages (from-to)98-109
Number of pages12
JournalCancer Letters
Volume268
Issue number1
DOIs
StatePublished - 8 Sep 2008
Externally publishedYes

Keywords

  • B7-H1 (PD-L1)
  • Costimulation
  • Interferon-γ
  • Pancreatic cancer

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