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
The G protein-coupled receptor ADGRE5(CD97)binds to various metabolites that play crucial regulatory roles in metabolism.However,its function in the antiviral innate immune response remains to be determined.In this st...The G protein-coupled receptor ADGRE5(CD97)binds to various metabolites that play crucial regulatory roles in metabolism.However,its function in the antiviral innate immune response remains to be determined.In this study,we report that CD97 inhibits virus-induced type-I interferon(IFN-I)release and enhances RNA virus replication in cells and mice.CD97 was identified as a new negative regulator of the innate immune receptor RIG-I,and RIG-1 degradation led to the suppression of the IFN-I signaling pathway.Furthermore,overexpression of CD97 promoted the ubiquitination of RIG-I,resulting in its degradation,but did not impact its mRNA expression.Mechanistically,CD97 upregulates RNF125 expression to induce RNF125-mediated RIG-I degradation via K48-linked ubiquitination at Lys181 after RNA virus infection.Most importantly,CD97-deficient mice are more resistant than wild-type mice to RNA virus infection.We also found that sanguinarine-mediated inhibition of CD97 effectively blocks VSV and SARS-CoV-2 replication.These findings elucidate a previously unknown mechanism through which CD97 negatively regulates RIG-I in the antiviral innate immune response and provide a molecular basis for the development of new therapeutic strategies and the design of targeted antiviral agents.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。
基金supported by grants from the National Natural Science Fund of China(32072834,31972665)Special fund support for Taishan Scholar Project(H.H,tspd20181207)Shandong Provincial Natural Science Foundation,China(ZR2021MC050),and Jinan Innovation Team(202228060).
文摘The G protein-coupled receptor ADGRE5(CD97)binds to various metabolites that play crucial regulatory roles in metabolism.However,its function in the antiviral innate immune response remains to be determined.In this study,we report that CD97 inhibits virus-induced type-I interferon(IFN-I)release and enhances RNA virus replication in cells and mice.CD97 was identified as a new negative regulator of the innate immune receptor RIG-I,and RIG-1 degradation led to the suppression of the IFN-I signaling pathway.Furthermore,overexpression of CD97 promoted the ubiquitination of RIG-I,resulting in its degradation,but did not impact its mRNA expression.Mechanistically,CD97 upregulates RNF125 expression to induce RNF125-mediated RIG-I degradation via K48-linked ubiquitination at Lys181 after RNA virus infection.Most importantly,CD97-deficient mice are more resistant than wild-type mice to RNA virus infection.We also found that sanguinarine-mediated inhibition of CD97 effectively blocks VSV and SARS-CoV-2 replication.These findings elucidate a previously unknown mechanism through which CD97 negatively regulates RIG-I in the antiviral innate immune response and provide a molecular basis for the development of new therapeutic strategies and the design of targeted antiviral agents.
