Aims: CD4+ CD25+ forkhead box P3 (FOXP3)+ Treg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (Treg), we conducted a retrospective study on 164 patients with hepatocellular carcinoma (HCC) who underwent curative hepatic resection. Methods: We investigated the number of tumor-infiltrating FOXP3+ Treg in formalin-fixed HCC specimens. The number of FOXP3+ Treg for each case was calculated as the total number of positive cells per 10 high-power fields (HPF) on light microscopy. Long-term survival rate after resection according to the number of FOXP3+ Treg was accessed by univariate and multivariate analyses. Results: The mean and median numbers of tumor-infiltrating Treg were 29.0 and 14 per 10 HPF for FOXP3+ Treg. The number of FOXP3+ Treg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high Treg counts (≥14, n = 84) than in those with low Treg counts (<14, n = 80) (13.6% vs. 25.7% at 5 years; P = 0.02). By multivariate analysis, the high Treg counts, presence of portal vein invasion, and elevation of preoperative aspartate aminotransferase level were independent predictive factors of tumor recurrence. Conclusions: The high number of tumor-infiltrating Treg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.
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