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

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-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.
Authors	Martin Loos, Nathalia A Giese, Jörg Kleeff, Thomas Giese, Matthias M Gaida, Frank Bergmann, Melanie Laschinger, Markus W Büchler, Helmut Friess
Journal	Cancer letters (Cancer Lett) Vol. 268 Issue 1 Pg. 98-109 (Sep 08 2008) ISSN: 0304-3835 [Print] Ireland
PMID	18486325 (Publication Type: Journal Article)
Chemical References	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
Topics	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, metabolism, mortality) Programmed Cell Death 1 Ligand 2 Protein Survival Analysis T-Lymphocytes, Regulatory (immunology) Up-Regulation

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