Abstract
B7-H4 is a recently identified member of the B7 family considered to negatively regulate the immune response, and has been associated with the occurrence and development of certain types of tumor. However, little is known regarding the importance of human B7-H4 expression in bladder urothelial carcinoma. In the present study, B7-H4 expression in the tissues and sera of patients with bladder urothelial carcinoma was investigated, along with the clinical significance. In addition, the effects of activated T-lymphocyte in vitro cytotoxicity in the BIU-87 bladder cancer cell line following the blockade of the B7-H4 signaling pathway were also analyzed. The results showed that in normal bladder tissues, B7-H4 was not detected, but in the bladder urothelial carcinoma tissue samples, B7-H4 was detected in 24/49 (49.0%) specimens. Additionally, positive B7-H4 expression was significantly associated with increased TNM stage and pathological grade (P<0.05). Compared with the healthy control group, the serum-B7-H4 (sB7-H4) concentrations in the patients were also significantly increased (P<0.05). The sB7-H4 concentrations in cases with high-grade histology were significantly higher than those in patients with low-grade histology (P<0.05). Following the blockade of the B7-H4 antigen in BIU-87 cells, the cytotoxic activity of activated T cells against such BIU-87 cells was significantly enhanced compared with that against the control BIU-87 cells. This occurred in a T cell density-dependent and blocking antibody dose-dependent manner. These observations suggest that B7-H4 is involved in tumor occurrence, and the development and immune escape of bladder urothelial carcinoma cells. Therefore, B7-H4 may be an important target in the diagnosis and/or treatment of bladder urothelial carcinoma.
Highlights
Bladder cancer (BCa) is one of the most common types of malignant tumor of the urinary system, worldwide
The present study focused on B7‐H4 expression in bladder urothelial carcinoma and investigated the association between B7‐H4 and immune escape mechanisms in this type of cancer
B7‐H4 expression was clearly associated with clinical stage and pathological grade, as the positive rate of B7‐H4 expression in patients at stage T2‐T4 was significantly higher than that in patients at stage Ta‐T1 (P
Summary
Bladder cancer (BCa) is one of the most common types of malignant tumor of the urinary system, worldwide. In Western countries, BCa is the fifth most common type of cancer and is a chronic disease with varying oncological outcomes. The most commonly diagnosed histological type of BCa is urothelial carcinoma (or transitional cell carcinoma), which accounts for ~95% cases. In urothelial carcinoma, >70% cases are classified as non‐muscle‐invasive bladder cancer (NMIBC). Remission is achieved in the majority of NMIBC cases by transurethral resection of the bladder tumor; after 3‐5 years, the recurrence rate reaches 60‐90%. Muscle‐invasive BCa cases require partial or total bladder resection. A number of clinicians have expressed concern regarding how to inhibit the recurrence and progression of BCa
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