B7‑H4 expression in bladder urothelial carcinoma and immune escape mechanisms

Liu,Wei‑Hui; Chen,Ya‑Yu; Zhu,Shao‑Xing; Li,Yi‑Ning; Xu,Yi‑Peng; Wu,Xue‑Jing; Guo,Yi‑Hong; Wang,Jia‑Liang

doi:10.3892/ol.2014.2522

B7‑H4 expression in bladder urothelial carcinoma and immune escape mechanisms

Authors:
- Wei‑Hui Liu
- Ya‑Yu Chen
- Shao‑Xing Zhu
- Yi‑Ning Li
- Yi‑Peng Xu
- Xue‑Jing Wu
- Yi‑Hong Guo
- Jia‑Liang Wang
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Affiliations: Department of Urinary Surgery, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China, Department of Stomatology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China, Department of Urinary Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
Published online on: September 11, 2014 https://doi.org/10.3892/ol.2014.2522
Pages: 2527-2534

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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.

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