Skewed T-helper (Th)1/2- and Th17/T regulatory‑cell balances in patients with renal cell carcinoma

Li,Long; Yang,Cheng; Zhao,Zitong; Xu,Bin; Zheng,Minghuan; Zhang,Chao; Min,Zhihui; Guo,Jianming; Rong,Ruiming

doi:10.3892/mmr.2014.2778

Skewed T-helper (Th)1/2- and Th17/T regulatory‑cell balances in patients with renal cell carcinoma

Authors:
- Long Li
- Cheng Yang
- Zitong Zhao
- Bin Xu
- Minghuan Zheng
- Chao Zhang
- Zhihui Min
- Jianming Guo
- Ruiming Rong
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Affiliations: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: October 27, 2014 https://doi.org/10.3892/mmr.2014.2778
Pages: 947-953
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The characterization of CD4+ T-cell subsets reflects the immune status and is important in the maintenance of tumorigenesis and homeostasis. To identify changes in the balance of T helper (Th)1, Th2, Th17 and regulatory T cells (Treg) in individuals with renal cell carcinoma (RCC), the present study investigated a total of 131 patients with RCC and 36 healthy volunteers. The number of CD4+ T‑bet+ cells, CD4+ GATA binding protein 3+ cells, CD4+ RAR-related orphan receptor γt+ cells, CD4+ CD25hi CD127lo CD45RA‑ cells and CD4+ CD25hi CD127lo CD45RA+ cells, defined as Th1, Th2, Th17, activated and naïve Treg cells, respectively, were detected in the peripheral blood using flow cytometric analysis. In addition, tumor‑infiltrating forkhead box P3 (Foxp3)+ cells were examined using immunohistochemistry. Compared with healthy volunteers, a significant decrease in the peripheral percentages of Th1, activated and naïve Treg cells was observed in patients with RCC, while those of the Th2 and Th17 cells were increased. In particular, as the tumor stage and grade progressed, the levels of Th1, activated and naïve Treg cells in the peripheral blood decreased; however, the levels of Th2 and Th17 cells increased. Furthermore, the number of tumor-infiltrating Foxp3+ cells increased with increasing tumor stage. These results demonstrated that the balance of Th1 and Th2 cells was skewed towards the Th2 profile and the balance of Th17 and Treg cells was skewed towards the Th17 profile in the peripheral blood of patients with renal cell carcinoma (RCC) and Treg cells were recruited to the tumor sites. Therefore, dysfunctional host anti‑tumor immunity was observed in patients with RCC, with a skewed Th1/Th2 and Th17/Treg balance.

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