The coexpression and clinical significance of costimulatory molecules B7-H1, B7-H3, and B7-H4 in human pancreatic cancer
Authors Chen Y, Sun J, Zhao H, Zhu D, Zhi Q, Song S, Zhang L, He S, Kuang Y, Zhang Z, Li D
Received 25 April 2014
Accepted for publication 9 June 2014
Published 19 August 2014 Volume 2014:7 Pages 1465—1472
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Yan Chen,1,* Jing Sun,2,* Hua Zhao,1 Dongming Zhu,1 Qiaoming Zhi,1 Shiduo Song,1 Lifeng Zhang,1 Songbing He,1 Yuting Kuang,1 Zixiang Zhang,1 Dechun Li1
1Department of General Surgery, First Affiliated Hospital of Soochow University, 2Department of Immunology, Soochow University, Suzhou, People's Republic of China
*These authors contributed equally to this work
Aim: We investigated the expression of the inhibitory costimulatory molecules B7-H1, B7-H3, and B7-H4 in human pancreatic cancer to define their clinical significance and mechanism in a tumor microenvironment.
Patients and methods: Sixty-three pancreatic cancer tissues and 12 normal pancreatic tissues were examined in our research. Patients were enrolled in the study between December 2000 and August 2010. Expression levels of the B7 family of molecules and densities of tumor-infiltrating lymphocytes in the tissues were characterized with immunohistochemical assays.
Results: More than 50% of the patients expressed B7-H1 and B7-H4, and nearly 100% of the patients expressed B7-H3. B7-H1 expression was correlated with tumor size, B7-H3 expression was correlated with lymph-node metastasis and differentiation grade, and B7-H4 expression was correlated with tumor size, lymph-node metastasis, and invasion depth. High B7-H4 expression was also correlated with poor survival in pancreatic cancer. We determined the value of these three B7 family molecules in the postoperative survival prognosis for patients with pancreatic cancer, and pancreatic cancer patients with less coexpression of the B7 family of molecules had a significantly higher survival rate. B7-H1 expression was found to be negatively related to the intensity of both CD3+ T cells and CD8+ T cells, and B7-H4 expression was negatively related to CD3+ T-cell infiltration intensity, but not to CD8+ T cells.
Conclusion: B7-H1, B7-H3, and B7-H4 are involved in pancreatic cancer progression, and their coexpression could be a valuable prognostic indicator. Negative regulation of T-cell infiltration might be the main mechanism of action of the B7 family of molecules in pancreatic cancer.
Keywords: pancreatic cancer, B7-H1, B7-H3, B7-H4, tumor-infiltrated T cell