Increased Frequency of CD4+CD25highFoxP3+ Regulatory T Cells in Patients with Hepatocellular Carcinoma
Increased Frequency of CD4+CD25highFoxP3+ Regulatory T Cells in Patients with Hepatocellular Carcinoma
复制标题
DOI：
10.1007/s00005-011-0127-0
复制
发表时间：
2011-08-01
影响因子：
3.2
通讯作者：
Long, Dan
中科院分区：
文献类型：
--
作者：
Feng, Xi;Li, Bo;Long, Dan
越来越多的证据表明，调节性T细胞(Treg)与抗肿瘤反应受损有关。然而，CD4(+)CD25(高)FoxP3(+)Treg与肝细胞癌的关系尚未得到很好的研究。用流式细胞仪检测肝癌患者和健康体检者外周血单个核细胞(PBMC)、肿瘤浸润性淋巴细胞(TIL)和肝切除肝淋巴细胞中CD4(+)CD25(高)FoxP3(+)Tregs的水平，并用H-3-胸腺嘧啶核苷掺入法检测它们对T细胞增殖的影响。采用酶联免疫吸附试验检测血清白介素10和转化生长因子β1水平。肝癌患者PBMCs中Tregs的表达频率高于健康人。同样，TIL中Tregs的频率高于肝淋巴细胞。另一方面，肝细胞癌患者的TIL和PBMC对H-3-胸腺嘧啶核苷的摄取与正常对照组相比显著降低。此外，与健康献血者相比，肝细胞癌患者血清IL-10和转化生长因子-β1水平显著升高。这项研究发现，在肝细胞癌患者中，CD4(+)CD25(高)FoxP3(+)Tregs的频率增加。血清IL-10、TGF-β1水平升高也与这些患者的抗肿瘤反应受损有关。需要进一步的努力来建立新的免疫治疗策略，旨在调节Treg来促进有能力的抗肿瘤反应。
Accumulating evidence suggests regulatory T cells (Tregs) are associated with impaired antitumor responses. However, the relationship between the CD4(+)CD25(high)FoxP3(+) Treg and hepatocellular carcinoma (HCC) has not been well investigated. Levels of CD4(+)CD25(high)FoxP3(+) Tregs in peripheral blood mononuclear cells (PBMCs) from HCC patients and healthy donors, tumor infiltrating lymphocytes (TILs) extracted from HCC, and hepatic lymphocytes extracted from resected liver were measured by flow cytometry, and their effects on T-cell proliferation was determined by H-3-thymidine incorporation. Serum levels of interleukin (IL)-10 and transforming growth factor (TGF)-beta 1 were measured by enzyme linked immunosorbent assay. The frequency of Tregs in PBMCs from HCC patients was higher than that from healthy donors. Similarly, the frequency of Tregs in TILs was higher than that of hepatic lymphocytes. On the other hand, the H-3-thymidine uptake by TILs and PBMCs from HCC patients was decreased drastically when compared to the counterparts from normal controls. Furthermore, serum IL-10 and TGF-beta 1 levels increased significantly in HCC patients when compared to the healthy donors. This study identified an increased frequency of CD4(+)CD25(high)FoxP3(+) Tregs in patients with HCC. The elevated serum IL-10, TGF-beta 1 levels also correlated with impaired antitumor responses in these patients. Further effort is needed to establish new immunotherapeutic strategies designed to modulate Tregs to promote a competent antitumor response.