B7-H4 expression and its role in interleukin-2/interferon treatment of clear cell renal cell carcinoma.
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.
Department of Urology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Yipeng
Y
Xu
Department of Urology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Shaoxing
S
Zhu
Department of Ultrasonography, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Mei
M
Song
Department of Urology, Fujian Medical University Second Affiliated Hospital, Quanzhou, Fujian 362000, P.R. China.
Weihui
W
Liu
Department of Urology, Lu'an Affiliated Hospital of Anhui Medical University, Lu'an, Anhui 237005, P.R. China.
Chengyi
C
Liu
Department of Urology, The Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
Yongsheng
Y
Li
Institute of Ophthalmology, Shandong Academy of Medical Sciences, Qingdao, Shandong 266071, P.R. China.
Min
M
Wang
B7-H4; clear cell renal cell carcinoma; cytokines; tumor immunity