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

• Published in: Cancer letters 2008-09, Vol.268 (1), p.98-109
• Main Authors: Loos, Martin, Giese, Nathalia A, Kleeff, Jörg, Giese, Thomas, Gaida, Matthias M, Bergmann, Frank, Laschinger, Melanie, W.Büchler, Markus, Friess, Helmut
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; Apoptosis; B7-1 Antigen - metabolism; B7-2 Antigen - metabolism; B7-H1 (PD-L1); Cancer therapies; Cell cycle; Cell Line, Tumor; Clinical trials; Costimulation; CTLA-4 Antigen; Cytokines; Cytokines - metabolism; Cytotoxicity; Esophageal cancer; Gene expression; Hematology, Oncology and Palliative Medicine; Humans; Immune system; Interferon-gamma - metabolism; Interferon-γ; Ligands; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Medical prognosis; Medical research; Mortality; Pancreatic cancer; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - mortality; Programmed Cell Death 1 Ligand 2 Protein; Studies; Survival Analysis; T cell receptors; T-Lymphocytes, Regulatory - immunology; Tumors; Up-Regulation
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2008.03.056

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.