Regulatory T cells and TGF-β1 in clinically localized renal cell carcinoma: Comparison with age-matched healthy controls

Purpose: We investigated the proportion of regulatory T cells (Treg cells) in the peripheral blood (PB) and among tumor-infiltrating lymphocytes (TILs) of patients with renal cell carcinoma (RCC) compared with age-matched healthy controls (HCs). We also assessed the presence of several immunomodulatory cytokines in these patients. Methods: The proportion of Treg cells in the PB of 59 patients with clinically localized RCC and 65 HCs, as well as the prevalence of Treg cells among TILs and lymphocytes in normal kidney tissue, were evaluated by flow cytometry using specific monoclonal antibodies recognizing CD4⁺, CD25⁺, and Foxp3⁺ markers. In addition, the levels of transforming growth factor (TGF)-β1, interleukin-6, tumor necrosis factor-α, and interferon-γ were determined using standard enzyme-linked immunosorbent assay. Results: There was no difference between the mean percentage of Treg cells in the PB of patients with RCC and HCs (P = 0.148). However, the proportion of Treg cells showed a significant positive correlation with tumor size (r = 0.295, P = 0.029), with the percentage of PB Treg cells significantly higher in patients with RCC with large tumors (≥7. cm) than in HCs (4.6±5.8% vs. 1.9±2.6%, P = 0.023). There was no statistically significant difference in the percentage of Treg cells among TILs and lymphocytes in normal kidney tissue (P = 0.629). The mean TGF-β1 level in patients with RCC was statistically significantly higher than in HCs (P<0.001). Conclusions: In this study, we provide evidence for an increased proportion of Treg cells in the PB of clinically localized patients with RCC with substantial tumor burden and a higher level of TGF-β1 compared with age-matched HCs.