Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Me...Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.展开更多
目的:基于Meta分析的方法评估DEFB1基因rs11362(C/T)多态性与龋病易感性的关系。方法:通过检索Web of Science、Pubmed,Embase、Springerlink、中国知网(CNKI)、万方(WangFang),维普(VIP)及中国生物医学文献数据库(CBM)等数据库,检索年...目的:基于Meta分析的方法评估DEFB1基因rs11362(C/T)多态性与龋病易感性的关系。方法:通过检索Web of Science、Pubmed,Embase、Springerlink、中国知网(CNKI)、万方(WangFang),维普(VIP)及中国生物医学文献数据库(CBM)等数据库,检索年限自数据库建库至2020年12月1日,对DEFB1基因rs11362多态性和龋病易感性的相关文献进行数据提取和质量评价,以OR和95%CI为效应指标,运用Stata 15.0软件进行rs11362多态性与龋病易感性的Meta分析。结果:共纳入72项病例对照研究,涉及905例龋病患者,791例对照人群,Meta分析结果表明DEFB1基因rs11362多态性与龋病发病风险的相关性无统计学意义(P>0.05)。结论:现有证据显示DEFB1基因rs11362多态性与龋病易感性无关。展开更多
基金supported by the National Natural Science Foundation of China(No.81972681,82103677)Tianjin Education Commission Research Plan Project(No.2021KJ201)+1 种基金Shenzhen High-level Hospital Construction Fund(No.G2022139)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-009A).
文摘Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.
文摘目的:基于Meta分析的方法评估DEFB1基因rs11362(C/T)多态性与龋病易感性的关系。方法:通过检索Web of Science、Pubmed,Embase、Springerlink、中国知网(CNKI)、万方(WangFang),维普(VIP)及中国生物医学文献数据库(CBM)等数据库,检索年限自数据库建库至2020年12月1日,对DEFB1基因rs11362多态性和龋病易感性的相关文献进行数据提取和质量评价,以OR和95%CI为效应指标,运用Stata 15.0软件进行rs11362多态性与龋病易感性的Meta分析。结果:共纳入72项病例对照研究,涉及905例龋病患者,791例对照人群,Meta分析结果表明DEFB1基因rs11362多态性与龋病发病风险的相关性无统计学意义(P>0.05)。结论:现有证据显示DEFB1基因rs11362多态性与龋病易感性无关。
