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Document type:
Journal Article; Article
Author(s):
Loos, M; Giese, NA; Kleeff, J; Giese, T; Gaida, MM; Bergmann, F; Laschinger, M; W Büchler, M; Friess, H
Title:
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.
Journal title abbreviation:
Cancer Lett
Year:
2008
Journal volume:
268
Journal issue:
1
Pages contribution:
98-109
Language:
eng
Fulltext / DOI:
doi:10.1016/j.canlet.2008.03.056
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/18486325
Print-ISSN:
0304-3835
TUM Institution:
Chirurgische Klinik und Poliklinik
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