Involvement of T helper type 17 and regulatory T cell activity in tumour immunology of bladder carcinoma

Abstract

T helper type 17 (Th17) and regulatory T cells (T(reg) ) play an important role in the pathogenesis of inflammation and autoimmune disorders. Recent studies have suggested that they also had an impact on tumour immunology. However, the relationship between Th17 and T(reg) cells in the pathogenesis of bladder carcinoma is still unclear. Flow cytometry was used to analyse the numbers, phenotype and cytokine production of Th17 cells in peripheral blood and tumour tissue from bladder carcinoma patients, in parallel with analysis of T(reg) cells. The suppressor capacity of T(reg) and the potential effects of interleukin (IL)-2 on the differentiation of Th17 and T(reg) cells in vitro were studied in a T cell stimulation and suppression assays. The results were as follows: Th17 cells were enriched in the tumours of patients with bladder carcinoma compared with the peripheral blood of patients and controls; patients with bladder carcinoma had a higher proportion of T(reg) cells in peripheral blood compared with healthy controls and nearly all patients examined showed a relative enrichment of tumour-infiltrating T(reg) with respect to peripheral blood; there appeared to be an inverse relationship between tumour-infiltrating Th17 and T(reg) cells; IL-2 could convert tumour-infiltrating T(reg) cells cultured in the presence of the autologous irradiated CD3(-) fraction into Th17 cells, down-regulate forkhead box P2 expression and suppressive capacity of T(reg) cells. This study is the first to define the frequency and characteristics of Th17 cells in bladder carcinoma. We suggest that the balance between Th17 and T(reg) cells may be involved in the development or progression of bladder carcinoma.