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

Sasaki, A.; Tanaka, F.; Mimori, K.; Inoue, H.; Kai, S.; Shibata, K.; Ohta, M.; Kitano, S.; Mori, M.

doi:10.1016/j.ejso.2007.08.008

« Previous Next »European Journal of Surgical Oncology
Volume 34, Issue 2 , Pages 173-179, February 2008

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

A. Sasaki
- Department of Surgery, National Hospital Organization Miyazaki Hospital, 19403-4 Kawaminami-machi, Miyazaki 889-1301, Japan
- Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan
- Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
- Corresponding author. Department of Surgery, National Hospital Organization Miyazaki Hospital, 19403-4 Kawaminami-machi, Miyazaki 889-1301, Japan. Tel.: +81 983 27 1036; fax: +81 983 27 5033.
F. Tanaka
- Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan
K. Mimori
- Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan
H. Inoue
- Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan
S. Kai
- Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
K. Shibata
- Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
M. Ohta
- Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
S. Kitano
- Department of Surgery I, Oita University Faculty of Medicine, 1-1 Yufu 889-5593, Japan
M. Mori
- Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan

Accepted 21 August 2007.

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.