Foxp3+ 调节性 T 细胞与慢性乙型肝炎的自然史和肝细胞癌的不良预后相关。
Foxp3+ regulatory T cells are associated with the natural history of chronic hepatitis B and poor prognosis of hepatocellular carcinoma.
机构信息
Department of Gastroenterology and Hepatology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
出版信息
Liver Int. 2012 Apr;32(4):644-55. doi: 10.1111/j.1478-3231.2011.02675.x. Epub 2011 Nov 28.
BACKGROUND
Recent studies have focused on regulatory T cells (Tregs) in chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) and they were also conducted independently of each other.
AIMS
This study tried to characterize Tregs in blood and tumour infiltration, and to explore the correlations between Tregs and the context of chronic hepatitis B in HCC patients.
METHODS
The liver-resident Tregs and CD8(+) T cells on core biopsy were investigated using immunohistochemistry staining in individuals (n = 209) with CHB (n = 47), HCC (n = 137) or healthy controls (n = 25). Circulating Tregs were detected in the above patients with CHB (n = 27) or HCC (n = 101) by flow cytometry.
RESULTS
The number of tumour-infiltrating and circulating FoxP3(+) Tregs was significantly high in patients with CHB (P < 0.001). However, there were fewer intratumoural Tregs in patients with advanced HCC than those in patients with early stage HCC (P = 0.043); In contrast, the circulating Tregs frequency increased during the progression of HCC (P = 0.024). Increased tumour-infiltrating and circulating FoxP3(+) Tregs were associated with poor overall survival (P = 0.041, 0.002 respectively) and a shorter time to recurrence (P = 0.049, 0.002 respectively) in patients with early stage HCC. Tumour-infiltrating Foxp3 + Tregs were related to chronic hepatitis B natural history in HCC (P = 0.012). Neither tumour-infiltrating CD8(+) T cells nor balance of intratumoural Tregs and CD8(+) T cells correlated with prognosis of HCC.
CONCLUSIONS
Increased Foxp3(+) Tregs may represent a prognostic predictor in patients with early stage HCC. The CHB natural history influenced density of tumour-infiltrating Tregs in hepatocellular carcinoma patients with chronic hepatitis B viruses infection.
背景
最近的研究集中在慢性乙型肝炎（CHB）和肝细胞癌（HCC）中的调节性 T 细胞（Tregs），并且这些研究也是相互独立进行的。
目的
本研究试图对血液和肿瘤浸润中的 Tregs 进行特征描述，并探讨 Tregs 与 HCC 患者慢性乙型肝炎背景之间的相关性。
方法
采用免疫组织化学染色法对 209 例个体（CHB 患者 47 例、HCC 患者 137 例和健康对照者 25 例）的肝固有 Tregs 和 CD8(+)T 细胞进行研究。通过流式细胞术检测 CHB（n=27）或 HCC（n=101）患者中的循环 Tregs。
结果
CHB 患者的肿瘤浸润和循环 FoxP3(+)Tregs 数量明显较高（P<0.001）。然而，晚期 HCC 患者肿瘤内 Tregs 数量少于早期 HCC 患者（P=0.043）；相反，在 HCC 进展过程中循环 Tregs 频率增加（P=0.024）。肿瘤浸润和循环 FoxP3(+)Tregs 增加与早期 HCC 患者的总生存不良（P=0.041，0.002）和复发时间较短（P=0.049，0.002）相关。肿瘤浸润 Foxp3+Tregs 与 HCC 中的慢性乙型肝炎自然史相关（P=0.012）。肿瘤内 CD8(+)T 细胞或肿瘤内 Tregs 和 CD8(+)T 细胞的平衡均与 HCC 的预后无关。
结论
Foxp3(+)Tregs 增加可能代表早期 HCC 患者的预后预测指标。乙型肝炎病毒感染的慢性乙型肝炎患者中，肿瘤浸润 Tregs 的密度受慢性乙型肝炎自然史的影响。
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