The prognostic value of peritumoral regulatory T cells and its correlation with intratumoral cyclooxygenase‐2 expression in clear cell renal cell carcinoma

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Abstract
OBJECTIVE: To investigate the prognostic value of regulatory T cells (Tregs) and its correlation with cyclooxygenase‐2 (COX‐2) expression in clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: CD4+, Foxp3+ tumour‐infiltrating lymphocytes and tumour COX‐2 expression were assessed by immunohistochemistry in tissue microarrays containing RCC from 125 patients. Prognostic effects of low and high expression were evaluated by Cox regression and Kaplan–Meier analysis using the median values as thresholds. The expression of Tregs and COX‐2 were compared with the clinicopathological variables. In addition, Tregs and its correlation with COX‐2 expression was also analysed. RESULTS: Peritumoral Tregs were positively correlated with intratumoral COX‐2 expression (Spearman rank correlation 0.336, P < 0.001). Peritumoral Tregs were associated with TNM stage ( P = 0.001) and tumour size ( P = 0.002), while intratumoral COX‐2 expression was associated with TNM stage ( P = 0.018) and grade ( P = 0.013). Using multivariate analysis, increased peritumoral Tregs, higher TNM stage (III + IV), larger tumour size (≥7 cm) and higher nuclear grade (III + IV) were independent predictors for significantly shorter overall survival and disease‐free survival. CONCLUSIONS: Increased peritumoral Tregs are associated with worse prognosis in clear cell RCC. The high intratumoral COX‐2 expression may be the underlying reason for the aberrant gathering of Tregs. These results suggest that clinical application of COX‐2 inhibitors may benefit those patients with higher intratumoral COX‐2 immunostaining by reducing the transformation of Tregs in RCC.

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