Increased frequency of CD4+ CD25+ FOXP3+ cells correlates with the progression of 4-nitroquinoline1-oxide-induced rat tongue carcinogenesis

OBJECTIVES: CD4+ CD25+ FoxP3+ T cells (Tregs) play an essential role in sustaining self-tolerance by negatively regulating immune responses. Increased frequencies of Tregs have been reported in a variety of human cancers. The aim of this study was to evaluate the prevalence of Tregs infiltration in the peripheral blood and regional lymph nodes during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide (4NQO). MATERIALS AND METHODS: Forty-eight Sprague–Dawley rats were divided into the control (n = 16) and experimental groups (n = 32) to which 4NQO in drinking water was administered. Flow cytometry was used to analyze the prevalence of Tregs in lymphocytes of peripheral blood and regional lymph nodes during 4NQO-induced rat tongue carcinogenesis. CD4+ CD25+ FoxP3+ cells were expressed as a percentage of the total CD4+ cells. RESULTS: The frequency of Tregs in peripheral blood from squamous cell carcinoma rats was significantly higher than controls (3.82 ± 0.62 versus 1.40 ± 0.31 %, P < 0.001). The proportion of Tregs was sequentially increased from moderate dysplasia to severe dysplasia and SCC (1.94 ± 0.72, 2.29 ± 0.82, and 3.82 ± 0.62 %, respectively). The frequency of Tregs in regional lymph nodes from squamous cell carcinoma rats was also significantly higher than normal rat mucosa (14.67 ± 3.09 versus 5.53 ± 2.07 %, P < 0.001). The percentage of Tregs was gradually increased in moderate dysplasia, severe dysplasia, and SCC groups (8.93 ± 1.74, 10.15 ± 0.86, 14.67 ± 3.09 %, respectively) as compared to control group (5.53 ± 2.07 %). CONCLUSION AND CLINICAL RELEVANCE: Tregs in peripheral blood and lymph nodes were associated with disease progression during 4NQO-induced rat tongue carcinogenesis. This study indicated that the upregulation of Tregs might play important role during oral mucosa malignant transformation.