B7‑H4 expression and its role in interleukin‑2/interferon treatment of clear cell renal cell carcinoma

Xu,Yipeng; Zhu,Shaoxing; Song,Mei; Liu,Weihui; Liu,Chengyi; Li,Yongsheng; Wang,Min

doi:10.3892/ol.2014.1961

B7‑H4 expression and its role in interleukin‑2/interferon treatment of clear cell renal cell carcinoma

Authors:
- Yipeng Xu
- Shaoxing Zhu
- Mei Song
- Weihui Liu
- Chengyi Liu
- Yongsheng Li
- Min Wang
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Affiliations: Department of Urology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Department of Ultrasonography, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Department of Urology, Fujian Medical University Second Affiliated Hospital, Quanzhou, Fujian 362000, P.R. China, Department of Urology, Lu'an Affiliated Hospital of Anhui Medical University, Lu'an, Anhui 237005, P.R. China, Department of Urology, The Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Institute of Ophthalmology, Shandong Academy of Medical Sciences, Qingdao, Shandong 266071, P.R. China
Published online on: March 11, 2014 https://doi.org/10.3892/ol.2014.1961
Pages: 1474-1478

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Abstract

The immunological mechanism mediated by T cells is the main therapeutic target in the treatment of renal cell carcinoma (RCC) with interleukin (IL)‑2 and interferon (IFN)‑α. The aim of the present study was to evaluate the role of B7‑H4 in the IL‑2, IFN‑α and IFN‑γ treatment of clear cell RCC (ccRCC). A total of 154 paraffin‑embedded ccRCC tissues were studied using immunohistochemistry, which subsequently indicated that positive B7‑H4 expression is associated with adverse clinical features in ccRCC. The effects of IL‑2, IFN‑α and IFN‑γ on B7‑H4 expression in a ccRCC cell line were evaluated at the mRNA and protein levels. In addition, the effect of B7‑H4 on the killing activity of T cells was detected. B7‑H4 expression was identified to be upregulated by IL‑2, IFN‑α and IFN‑γ, of which, IFN‑γ was the most capable. Additionally, blocking of B7‑H4/B7‑H4 ligand interactions may rescue the killing activity of T cells. Altogether, the observations of the current study showed that the immune escape pathway induced by B7‑H4 may be one of the most important reasons for the low efficacy of IL‑2 and IFN‑α and the inability to observe the efficacy of IFN‑γ in mRCC. This indicates that B7‑H4 may be used as a new molecular biology marker to select treatment options for patients with ccRCC.

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