Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8<sup>+</sup> T cell response. This process involves enhancement of...Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8<sup>+</sup> T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8<sup>+</sup> T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.展开更多
目的观察慢性乙肝病毒(HBV)感染者细胞免疫功能的变化,探讨病毒复制程度与细胞免疫功能的关系。方法应用流式细胞仪直接免疫荧光法检测230例乙肝病毒感染者5、0例正常对照外周血T细胞亚群百分率,用荧光定量PCR法检测乙肝感染者血清HBV ...目的观察慢性乙肝病毒(HBV)感染者细胞免疫功能的变化,探讨病毒复制程度与细胞免疫功能的关系。方法应用流式细胞仪直接免疫荧光法检测230例乙肝病毒感染者5、0例正常对照外周血T细胞亚群百分率,用荧光定量PCR法检测乙肝感染者血清HBV DNA。结果HBV感染者外周血CD4+T细胞百分率及CD4+/CD8+比值较正常对照组明显减低(36.8±10.6%vs 39.4±9.8%,P<0.05;1.5±0.8 vs 1.9±0.9,P<0.01),CD8+T细胞百分率明显升高(27.9±8.3%vs 24.1±7.0%,P<0.01),而CD3+T细胞百分率无明显差异(70.2±10.3%vs 69.9±5.2%,P>0.05)。根据HBV感染者血清中HVB DVA载量的高低,将它们分为低拷贝组(103-104copies/ml),高拷贝组(105-108copies/ml)以及DNA阴性组(<102copies/ml)。低拷贝组和高拷贝组的CD4+T细胞百分率及CD4+/CD8+比值比对照组明显减低(36.4±10.9%vs 39.4±9.8%,P<0.05;36.4±10.9%vs 39.4±9.8P<0.05;1.5±0.9 vs 1.9±0.9,P<0.01;1.1±0.7 vs 1.9±0.9,P<0.01),高拷贝组的CD4+/CD8+比值比低拷贝组和DNA阴性组明显减低(1.1±0.7 vs 1.5±0.9,P<0.01;1.1±0.7 vs 1.6±0.8,P<0.01),CD8+细胞百分率明显高于对照组和DNA阴性组(29.4±8.4%vs 24.1±7.0%,P<0.01;29.4±8.4%vs 25.7±7.3%vs 24.1±7.0%P<0.05)。而CD3+T细胞百分率在各组之间没有明显差异存在(P>0.05),CD4+在低、高拷贝组及DNA阴性组之间虽无明显差异存在(P>0.05),但随着DNA复制的增加,CD4+呈逐渐减少趋势。结论HBV感染可导致感染者细胞免疫功能的改变,HBA DNA复制增加进一步加重乙肝病毒感染者T细胞亚群的率乱,CD4+/CD8+比值的动态变化可及时提示临床HBV感染者细胞免疫功能的变化并加强临床的临测。展开更多
目的探讨蓝芩口服液对慢性咽炎患者血清炎症细胞因子、免疫细胞亚群及临床症状的影响。方法2组均进行常规治疗,对照组在此基础上口服喉疾灵片3粒/次,3次/d,观察组口服蓝芩口服液20 m L/次,3次/d,2组患者均7 d为1个疗程,连用3个疗程,检...目的探讨蓝芩口服液对慢性咽炎患者血清炎症细胞因子、免疫细胞亚群及临床症状的影响。方法2组均进行常规治疗,对照组在此基础上口服喉疾灵片3粒/次,3次/d,观察组口服蓝芩口服液20 m L/次,3次/d,2组患者均7 d为1个疗程,连用3个疗程,检测治疗前后血清白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)水平,外周血T淋巴细胞亚群及B细胞数,观察2组临床症状改善情况及不良反应情况。结果治疗后2组血清IL-2、TNF-α水平较治疗前改善,改善程度观察组优于对照组,差异有统计学意义(P<0.05);治疗后CD3、CD4、CD4/CD8及B细胞数均较治疗前改善,且观察组优于对照组,差异具有统计学意义(P<0.05);观察组咽喉部疼痛、异物感、干痒、咳嗽等改善时间明显短于对照组,差异具有统计学意义(P<0.05);观察组有2例轻度腹泻,停药后自行缓解,对照组未见明显不良反应。结论蓝芩口服液有较好的抗炎、抗病毒及增强免疫作用,可以有效缓解慢性咽炎症状。展开更多
基金Supported by "Instituto de Salud Carlos Ⅲ",Spain& "European Regional Development Fund(ERDF)a way of making Europe",No.PI12/00130 and No.PI15/00074and"Gilead Spain&Instituto de Salud Carlos Ⅲ",No.GLD14_00217
文摘Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8<sup>+</sup> T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8<sup>+</sup> T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.
文摘目的观察慢性乙肝病毒(HBV)感染者细胞免疫功能的变化,探讨病毒复制程度与细胞免疫功能的关系。方法应用流式细胞仪直接免疫荧光法检测230例乙肝病毒感染者5、0例正常对照外周血T细胞亚群百分率,用荧光定量PCR法检测乙肝感染者血清HBV DNA。结果HBV感染者外周血CD4+T细胞百分率及CD4+/CD8+比值较正常对照组明显减低(36.8±10.6%vs 39.4±9.8%,P<0.05;1.5±0.8 vs 1.9±0.9,P<0.01),CD8+T细胞百分率明显升高(27.9±8.3%vs 24.1±7.0%,P<0.01),而CD3+T细胞百分率无明显差异(70.2±10.3%vs 69.9±5.2%,P>0.05)。根据HBV感染者血清中HVB DVA载量的高低,将它们分为低拷贝组(103-104copies/ml),高拷贝组(105-108copies/ml)以及DNA阴性组(<102copies/ml)。低拷贝组和高拷贝组的CD4+T细胞百分率及CD4+/CD8+比值比对照组明显减低(36.4±10.9%vs 39.4±9.8%,P<0.05;36.4±10.9%vs 39.4±9.8P<0.05;1.5±0.9 vs 1.9±0.9,P<0.01;1.1±0.7 vs 1.9±0.9,P<0.01),高拷贝组的CD4+/CD8+比值比低拷贝组和DNA阴性组明显减低(1.1±0.7 vs 1.5±0.9,P<0.01;1.1±0.7 vs 1.6±0.8,P<0.01),CD8+细胞百分率明显高于对照组和DNA阴性组(29.4±8.4%vs 24.1±7.0%,P<0.01;29.4±8.4%vs 25.7±7.3%vs 24.1±7.0%P<0.05)。而CD3+T细胞百分率在各组之间没有明显差异存在(P>0.05),CD4+在低、高拷贝组及DNA阴性组之间虽无明显差异存在(P>0.05),但随着DNA复制的增加,CD4+呈逐渐减少趋势。结论HBV感染可导致感染者细胞免疫功能的改变,HBA DNA复制增加进一步加重乙肝病毒感染者T细胞亚群的率乱,CD4+/CD8+比值的动态变化可及时提示临床HBV感染者细胞免疫功能的变化并加强临床的临测。
文摘目的探讨蓝芩口服液对慢性咽炎患者血清炎症细胞因子、免疫细胞亚群及临床症状的影响。方法2组均进行常规治疗,对照组在此基础上口服喉疾灵片3粒/次,3次/d,观察组口服蓝芩口服液20 m L/次,3次/d,2组患者均7 d为1个疗程,连用3个疗程,检测治疗前后血清白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)水平,外周血T淋巴细胞亚群及B细胞数,观察2组临床症状改善情况及不良反应情况。结果治疗后2组血清IL-2、TNF-α水平较治疗前改善,改善程度观察组优于对照组,差异有统计学意义(P<0.05);治疗后CD3、CD4、CD4/CD8及B细胞数均较治疗前改善,且观察组优于对照组,差异具有统计学意义(P<0.05);观察组咽喉部疼痛、异物感、干痒、咳嗽等改善时间明显短于对照组,差异具有统计学意义(P<0.05);观察组有2例轻度腹泻,停药后自行缓解,对照组未见明显不良反应。结论蓝芩口服液有较好的抗炎、抗病毒及增强免疫作用,可以有效缓解慢性咽炎症状。
