目的:检测食管鳞癌患者外周血中程序性死亡分子1(programmed cell death 1,PD-1)、程序性死亡分子1配体(programmed cell death ligand 1,PD-L1)及IFN-γ表达情况,并分析其临床意义。方法选取2016年6月至2017年4月河北医科大学第四医院...目的:检测食管鳞癌患者外周血中程序性死亡分子1(programmed cell death 1,PD-1)、程序性死亡分子1配体(programmed cell death ligand 1,PD-L1)及IFN-γ表达情况,并分析其临床意义。方法选取2016年6月至2017年4月河北医科大学第四医院胸外科90例食管鳞状细胞癌患者(其中50例患者行手术治疗)和40例健康对照者为研究对象,收集研究其外周血液标本,采用酶联免疫吸附方法检测血清中可溶性PD-1(sPD-1)、可溶性PD-L1(sPD-L1)及IFN-γ的表达水平。采用SPSS 24.0软件对数据进行检验和相关性分析。结果:食管鳞癌组血清中sPD-1、sPD-L1及IFN-γ水平均明显高于正常对照组(P<0.05);食管鳞癌组手术前血清sPD-L1、IFN-γ水平均明显高于术后(P<0.05),而sPD-1水平两组比较无明显差异(P>0.05)。sPD-1、sPD-L1的表达水平与临床病理特征无明显相关(P>0.05),IFN-γ的表达水平与淋巴结转移情况相关(P<0.05),与T分期、TNM分期、肿瘤体积大小、肿瘤部位、组织分化程度、性别、年龄无明显相关(P>0.05)。血清中sPD-L1表达水平与IFN-γ无明显相关(P>0.05)。结论:食管鳞癌患者血清中sPD-L1较正常人表达升高,且术后表达较术前减少,说明血清中sPD-L1表达水平与病情发展变化有一定相关性。展开更多
程序性死亡分子1(programmed death-1,PD-1)/PD-1的配体(programmed death ligand,PD-L)属于抑制性共刺激分子,能对免疫反应的产生起负调节作用。PD-1在慢性感染性疾病中的功能缺陷型CD8+T细胞上高表达,导致功能性CD8+T细胞的功能受损,...程序性死亡分子1(programmed death-1,PD-1)/PD-1的配体(programmed death ligand,PD-L)属于抑制性共刺激分子,能对免疫反应的产生起负调节作用。PD-1在慢性感染性疾病中的功能缺陷型CD8+T细胞上高表达,导致功能性CD8+T细胞的功能受损,包括细胞增殖、细胞因子分泌和杀伤能力。在肿瘤、自身免疫性疾病和感染性疾病中,PD-1/PD-L参与免疫反应的调节,抑制抗瘤及抗病毒免疫反应,阻断此通路后可以恢复特异性CD8+T细胞的部分功能,因此,PD-1/PD-L通路可能与肿瘤细胞免疫逃避和病毒感染疾病慢性化有关。展开更多
Programmed cell death 1（PD-1）/programmed cell death 1 ligand（PD-L1） blockade has shown promising effects in cancer immunotherapy. Removing the so-called ＂brakes＂ on T cell immune responses by blocking the PD-1/P...Programmed cell death 1（PD-1）/programmed cell death 1 ligand（PD-L1） blockade has shown promising effects in cancer immunotherapy. Removing the so-called ＂brakes＂ on T cell immune responses by blocking the PD-1/PDL1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer patients.However, 30%–60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site,immunosuppressive factors in the tumor microenvironment（TME）, and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.展开更多
Cancer immunotherapy has been widely recognized as a powerful approach to fight cancers.To date,over 50 phase III trials in cancer immunotherapy are in progress.Among the many immunotherapy approaches,immune checkpoin...Cancer immunotherapy has been widely recognized as a powerful approach to fight cancers.To date,over 50 phase III trials in cancer immunotherapy are in progress.Among the many immunotherapy approaches,immune checkpoint therapy has attracted considerable attention.The reported clinical success of targeting the T cell immune checkpoint receptors PD-1 or CTLA4 by antibodies blockade in advanced stages of cancers has demonstrated the importance of immune modulation.But antibodies-based immunotherapy confronted with some disadvantages,such as immunogenicity,stability,membrane permeability,and production cost.Therefore,alternative approaches including small-molecule-regulated immune response are being introduced.In this review,we focused on some of the key intracellular pathways where small-molecule therapeutic is potential and attractive,which highlights the great potential of natural products in this field.展开更多
PD-1（programmed cell death 1）是近年新发现的一个负性共刺激信号分子，其配体为PD-LI和PD—12，同属于CD28／B7家族。PD-1／PD-L通路能削弱、限制和／或终止T细胞和APC等细胞的活化及效应功能，在慢性HBV感染的发病机制中发挥了重...PD-1（programmed cell death 1）是近年新发现的一个负性共刺激信号分子，其配体为PD-LI和PD—12，同属于CD28／B7家族。PD-1／PD-L通路能削弱、限制和／或终止T细胞和APC等细胞的活化及效应功能，在慢性HBV感染的发病机制中发挥了重要作用。展开更多
文摘目的:检测食管鳞癌患者外周血中程序性死亡分子1(programmed cell death 1,PD-1)、程序性死亡分子1配体(programmed cell death ligand 1,PD-L1)及IFN-γ表达情况,并分析其临床意义。方法选取2016年6月至2017年4月河北医科大学第四医院胸外科90例食管鳞状细胞癌患者(其中50例患者行手术治疗)和40例健康对照者为研究对象,收集研究其外周血液标本,采用酶联免疫吸附方法检测血清中可溶性PD-1(sPD-1)、可溶性PD-L1(sPD-L1)及IFN-γ的表达水平。采用SPSS 24.0软件对数据进行检验和相关性分析。结果:食管鳞癌组血清中sPD-1、sPD-L1及IFN-γ水平均明显高于正常对照组(P<0.05);食管鳞癌组手术前血清sPD-L1、IFN-γ水平均明显高于术后(P<0.05),而sPD-1水平两组比较无明显差异(P>0.05)。sPD-1、sPD-L1的表达水平与临床病理特征无明显相关(P>0.05),IFN-γ的表达水平与淋巴结转移情况相关(P<0.05),与T分期、TNM分期、肿瘤体积大小、肿瘤部位、组织分化程度、性别、年龄无明显相关(P>0.05)。血清中sPD-L1表达水平与IFN-γ无明显相关(P>0.05)。结论:食管鳞癌患者血清中sPD-L1较正常人表达升高,且术后表达较术前减少,说明血清中sPD-L1表达水平与病情发展变化有一定相关性。
文摘程序性死亡分子1(programmed death-1,PD-1)/PD-1的配体(programmed death ligand,PD-L)属于抑制性共刺激分子,能对免疫反应的产生起负调节作用。PD-1在慢性感染性疾病中的功能缺陷型CD8+T细胞上高表达,导致功能性CD8+T细胞的功能受损,包括细胞增殖、细胞因子分泌和杀伤能力。在肿瘤、自身免疫性疾病和感染性疾病中,PD-1/PD-L参与免疫反应的调节,抑制抗瘤及抗病毒免疫反应,阻断此通路后可以恢复特异性CD8+T细胞的部分功能,因此,PD-1/PD-L通路可能与肿瘤细胞免疫逃避和病毒感染疾病慢性化有关。
基金supported by grants from the National Natural Science Foundation of China (No. 81171986)the Ministry of Public Health (No. 201501004)
文摘Programmed cell death 1（PD-1）/programmed cell death 1 ligand（PD-L1） blockade has shown promising effects in cancer immunotherapy. Removing the so-called ＂brakes＂ on T cell immune responses by blocking the PD-1/PDL1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer patients.However, 30%–60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site,immunosuppressive factors in the tumor microenvironment（TME）, and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.
基金supported financially by the funding of Exploitation and Utilization of Abundant Natural Products from Plants from Kunming Institute of Botany(KIB2017009)the National Natural Science Foundation of China(U1402227)+2 种基金the 100 Talents Program of the Chinese Academy of Sciences(Y.Li)the Program of Recruited Top Talent of Sciences and Technology of Yunnan Province(2009CI120)the Independent Program of Key Laboratory of Natural Pharmaceutical Chemistry of Yunnan Province(Y.Li).
文摘Cancer immunotherapy has been widely recognized as a powerful approach to fight cancers.To date,over 50 phase III trials in cancer immunotherapy are in progress.Among the many immunotherapy approaches,immune checkpoint therapy has attracted considerable attention.The reported clinical success of targeting the T cell immune checkpoint receptors PD-1 or CTLA4 by antibodies blockade in advanced stages of cancers has demonstrated the importance of immune modulation.But antibodies-based immunotherapy confronted with some disadvantages,such as immunogenicity,stability,membrane permeability,and production cost.Therefore,alternative approaches including small-molecule-regulated immune response are being introduced.In this review,we focused on some of the key intracellular pathways where small-molecule therapeutic is potential and attractive,which highlights the great potential of natural products in this field.
