Tumor cells induce an immunosuppressive microen-vironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxyge...Tumor cells induce an immunosuppressive microen-vironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase(IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma(HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis. HCC associated fibroblasts stimulate natural killer cells dysfunction through prostaglandin E2 and subsequently IDO promotes favorable condition for tumor metastasis. IDO up-regulation induces immuno-suppression and may enhance the risk of hepatitis C virus and hepatitis B virus induced HCC. Therefore, IDO inhibitors as adjuvant therapeutic agents may have clinical implications in HCC. This review proposes future prospects of IDO not only as a therapeutic target but also as a prognostic marker for HCC.展开更多
目的:通过细胞培养和在体实验探讨吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)基因转染后对肝癌细胞凋亡的影响及相关细胞免疫机制的研究。方法:提取健康人外周血中的T细胞利用细胞培养和基因转染技术将T细胞和肝癌细胞混合...目的:通过细胞培养和在体实验探讨吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)基因转染后对肝癌细胞凋亡的影响及相关细胞免疫机制的研究。方法:提取健康人外周血中的T细胞利用细胞培养和基因转染技术将T细胞和肝癌细胞混合培养。实验分为6组:根据是否加入D-1-MT分为未干预组和干预组,每组根据培养细胞的不同又分为T细胞与HepG2细胞组、T细胞与pcDNA3.1-HepG2细胞组、T细胞与pcDNA3.1-IDO-HepG2细胞组。于混合培养2天后应用流式细胞术、MTT法检测各组中HepG2细胞的凋亡情况和T细胞抗HepG2细胞的细胞毒活性。在混合培养5天后应用流式细胞术检测调节性T细胞(Regulatory T cell,Treg)的比例。并建立人肝癌细胞小鼠模型,用流式细胞仪检测荷瘤小鼠外周血中Treg细胞的比例。结果:1.混合培养2天后,转染IDO基因的肝癌细胞其凋亡率和T细胞抗HepG2细胞的细胞毒活性均明显降低,分别为(1.65±0.14)%和(35.00±2.20)%(p<0.05);加入1-MT干预后,以上指标均明显高于干预前,且干预前后比较有明显的统计学意义(P<0.05)。2.混合培养5天后,IDO-HepG2细胞组Treg细胞的比例明显升高(10.53±1.05)%,与其余两个未干预组比较有统计学意义(p<0.05);加1-MT干预后,Treg细胞比例均明显降低(p<0.05)。3.转染IDO的荷瘤小鼠模型中外周血Treg细胞比例明显升高(15.33±1.18)%,与其余两组比较有统计学意义(p<0.05)。结论:1.IDO可能通过增加调节性T细胞的比例来抑制肝癌细胞(HepG2细胞)的凋亡和T细胞的免疫毒性功能。1-MT可抑制IDO的这种作用。2.在体实验证实IDO的过量表达可提高外周血Treg细胞的比例。展开更多
文摘Tumor cells induce an immunosuppressive microen-vironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase(IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma(HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis. HCC associated fibroblasts stimulate natural killer cells dysfunction through prostaglandin E2 and subsequently IDO promotes favorable condition for tumor metastasis. IDO up-regulation induces immuno-suppression and may enhance the risk of hepatitis C virus and hepatitis B virus induced HCC. Therefore, IDO inhibitors as adjuvant therapeutic agents may have clinical implications in HCC. This review proposes future prospects of IDO not only as a therapeutic target but also as a prognostic marker for HCC.
文摘目的:通过细胞培养和在体实验探讨吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)基因转染后对肝癌细胞凋亡的影响及相关细胞免疫机制的研究。方法:提取健康人外周血中的T细胞利用细胞培养和基因转染技术将T细胞和肝癌细胞混合培养。实验分为6组:根据是否加入D-1-MT分为未干预组和干预组,每组根据培养细胞的不同又分为T细胞与HepG2细胞组、T细胞与pcDNA3.1-HepG2细胞组、T细胞与pcDNA3.1-IDO-HepG2细胞组。于混合培养2天后应用流式细胞术、MTT法检测各组中HepG2细胞的凋亡情况和T细胞抗HepG2细胞的细胞毒活性。在混合培养5天后应用流式细胞术检测调节性T细胞(Regulatory T cell,Treg)的比例。并建立人肝癌细胞小鼠模型,用流式细胞仪检测荷瘤小鼠外周血中Treg细胞的比例。结果:1.混合培养2天后,转染IDO基因的肝癌细胞其凋亡率和T细胞抗HepG2细胞的细胞毒活性均明显降低,分别为(1.65±0.14)%和(35.00±2.20)%(p<0.05);加入1-MT干预后,以上指标均明显高于干预前,且干预前后比较有明显的统计学意义(P<0.05)。2.混合培养5天后,IDO-HepG2细胞组Treg细胞的比例明显升高(10.53±1.05)%,与其余两个未干预组比较有统计学意义(p<0.05);加1-MT干预后,Treg细胞比例均明显降低(p<0.05)。3.转染IDO的荷瘤小鼠模型中外周血Treg细胞比例明显升高(15.33±1.18)%,与其余两组比较有统计学意义(p<0.05)。结论:1.IDO可能通过增加调节性T细胞的比例来抑制肝癌细胞(HepG2细胞)的凋亡和T细胞的免疫毒性功能。1-MT可抑制IDO的这种作用。2.在体实验证实IDO的过量表达可提高外周血Treg细胞的比例。
