Prognostic value of tumor-infiltrating FOXP3 + regulatory T cells in patients with hepatocellular carcinoma

Abstract

Aims CD4 + CD25 + forkhead box P3 (FOXP3) + T reg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (T reg), 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 + T reg in formalin-fixed HCC specimens. The number of FOXP3 + T reg 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 + T reg was accessed by univariate and multivariate analyses. Results The mean and median numbers of tumor-infiltrating T reg were 29.0 and 14 per 10 HPF for FOXP3 + T reg. The number of FOXP3 + T reg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high T reg counts (≥14, n = 84) than in those with low T reg counts (<14, n = 80) (13.6% vs. 25.7% at 5 years; P = 0.02). By multivariate analysis, the high T reg 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 T reg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.