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

Department of Surgery, National Hospital Organization Miyazaki Hospital, 19403-4 Kawaminami-machi, Miyazaki 889-1301, Japan.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology (Impact Factor: 3.01). 02/2008; 34(2):173-9. DOI: 10.1016/j.ejso.2007.08.008
Source: PubMed


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.
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.
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 (> or =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.
The high number of tumor-infiltrating T(reg) is an independent predictive factor of tumor recurrence after hepatic resection for HCC.

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    • "Results of this study also identified several other types of TILs within the tumor center as having a positive impact on prognosis, for example FoxP3. The prognostic role of Tregs seems to vary significantly by tumor type possibly indicating differential roles of these cells in a tissue-dependent manner [26]–[28]. In colorectal cancer, most studies are in line with our findings indicating that a high number of FoxP3 Tregs is a favourable prognostic factor for disease-free and overall survival time [10], [29], [30]. "
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    PLoS ONE 12/2010; 5(12):e14282. DOI:10.1371/journal.pone.0014282 · 3.23 Impact Factor
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    • "Regulatory T cells (Treg) play an essential role in controlling immune responses to self and non-self antigens. It has been reported that the tumor infiltrating Treg cells are associated with a poorer prognosis in some cancers by suppressing the proliferation of effector T lymphocyte (i.e., cytotoxic T lymphocyte (CTL)) to prohibit an adequate tumor-specific immune response, thus enabling tumor growth [18-23]. In contrast, other researchers have reported that the tumor infiltrating Treg cells are either linked to a better prognosis or did not affect prognosis in some malignancies such as follicular lymphoma and squamous cell carcinoma [24-26]. "
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