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...

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Bibliographic Details
Published in:Oncology letters 2014-05, Vol.7 (5), p.1474-1478
Main Authors: XU, YIPENG, ZHU, SHAOXING, SONG, MEI, LIU, WEIHUI, LIU, CHENGYI, LI, YONGSHENG, WANG, MIN
Format: Article
Language:English
Subjects:
B7-H4
Cancer
Carcinoma, Renal cell
Care and treatment
Cell culture
Cell growth
clear cell renal cell carcinoma
Cytokines
Flow cytometry
Genetic aspects
Health aspects
Immunotherapy
Interferon
Interleukins
Kidney cancer
Ligands
Lymphocytes
Medical prognosis
Multivariate analysis
Oncology
Studies
tumor immunity
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Summary: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.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2014.1961