Department of Hepatobiliary Surgery, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China.
Chin Med J (Engl). 2012 Mar;125(5):786-93.
Astragalus polysaccharides (APS), the main active extract from Astragalus membranaceus (a traditional Chinese medicinal herb), is associated with a variety of immunomodulatory activities. The purpose of the present study was to examine the effect of APS on the function of Treg cells in the tumor microenvironment of human hepatocellular carcinoma (HCC) and to identify the pharmacologic mechanism of APS responsible for the anti-chemotactic activity in CD4+CD25highTreg cells in tumor site of HCC.
The prevalence of Treg in fresh tissue samples from 31 patients with HCC after radicalhepatectomy was detected. CD4, CD25 and CD127 were selected as Treg cell makers to phenotype cell populations. The expression of FOXp3 mRNA was also analyzed. The migration and proliferation of Treg cells were observed. Interleukin (IL)-4, IL-10, IFN-γ and SDF-1 in cell supernatant were detected. For all tests, functions of Treg cells were evaluated after treatment with APS.
APS can inhibit the growth and proliferation of CD4+CD25+Treg cells in vitro in a dose- and time-dependent manner. APS may inhibit CD4+CD25+Treg cells through restoring the cytokine imbalance and reducing the expression of FOXp3 in local HCC microenvironments. SDF-1 played an important role in there recruitment of Treg cells into the tumor microenvironment of HCC. APS might have inhibiting effects on Treg cell migration by blocking SDF-1 or its receptor through the CXCR4/CXCL12 pathway.
The increase in numbers of tumor associated Treg cells might play a role in modulation of the immune response against HCC. APS can restore the cytokine balance in the tumor micro environment and suppress the expression of FOXp3 mRNA to inhibit the immune suppressive effects of Treg cells. The application of APS in the tumor microenvironment might act to enhance the anti-tumor effects of the immunotherapy-based methods, and consequently to increase the survival rate in HCC.
黄芪多糖（APS）是中药黄芪的主要活性提取物，具有多种免疫调节活性。本研究旨在探讨 APS 对人肝癌（HCC）肿瘤微环境中 Treg 细胞功能的影响，并确定 APS 抑制 HCC 肿瘤部位 CD4+CD25highTreg 细胞趋化活性的作用机制。
检测 31 例根治性肝切除术后 HCC 患者新鲜组织标本中 Treg 的发生率。选择 CD4、CD25 和 CD127 作为 Treg 细胞标志物来表型细胞群体。还分析了 FOXp3 mRNA 的表达。观察 Treg 细胞的迁移和增殖。检测细胞上清液中白细胞介素（IL）-4、IL-10、IFN-γ 和 SDF-1 的含量。所有试验均在 APS 处理后评估 Treg 细胞的功能。
APS 可在体外以剂量和时间依赖的方式抑制 CD4+CD25+Treg 细胞的生长和增殖。APS 可能通过恢复局部 HCC 微环境中的细胞因子失衡并降低 FOXp3 的表达来抑制 CD4+CD25+Treg 细胞。SDF-1 在 Treg 细胞募集到 HCC 肿瘤微环境中起着重要作用。APS 可能通过阻断 CXCR4/CXCL12 通路抑制 SDF-1 或其受体，从而对 Treg 细胞迁移产生抑制作用。
肿瘤相关 Treg 细胞数量的增加可能在调节 HCC 免疫反应中发挥作用。APS 可恢复肿瘤微环境中的细胞因子平衡，并抑制 FOXp3 mRNA 的表达，从而抑制 Treg 细胞的免疫抑制作用。APS 在肿瘤微环境中的应用可能有助于增强基于免疫疗法的方法的抗肿瘤作用，从而提高 HCC 的生存率。
