Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting tolerance.DC-10,a tolerogenic population of human IL-10-producing DCs characterized by ...Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting tolerance.DC-10,a tolerogenic population of human IL-10-producing DCs characterized by the expression of HLA-G and ILT4,play a pivotal role in promoting tolerance via T regulatory type 1(Tr1)cells.Thus far,the absence of markers that uniquely identify DC-10 has limited in vivo studies.By in vitro gene expression profiling of differentiated human DCs,we identified CD141 and CD163 as surface markers for DC-10.The coexpression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of DC-10 from the peripheral blood.CD14+CD16+CD141+CD163+cells isolated from the peripheral blood of healthy subjects(ex vivo DC-10)produced spontaneously and upon activation of IL-10 and limited levels of IL-12.Moreover,in vitro stimulation of allogeneic naive CD4+T cells with ex vivo DC-10 induced the differentiation of alloantigen-specific CD49b+LAG-3+Tr1 cells.Finally,ex vivo DC-10 and in vitro generated DC-10 exhibited a similar transcriptional profile,which are characterized by an anti-inflammatory and pro-tolerogenic signature.These results provide new insights into the phenotype and molecular signature of DC-10 and highlight the tolerogenic properties of circulating DC-10.These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.展开更多
Macrophages are among the most abundant immune cells in the tumor microenvironment, where they are known as tumor-associated macrophages （TAMs）. Substantial evidence indicates that TAMs generally play pro＇tumoral r...Macrophages are among the most abundant immune cells in the tumor microenvironment, where they are known as tumor-associated macrophages （TAMs）. Substantial evidence indicates that TAMs generally play pro＇tumoral roles in the primary as well as metastatic sites （Noy and Pollard, 2014）. TAMs are also known to interfere with several tumor therapeutic modalities, such as chemotherapy, irradiation, and immunotherapy. In general, depletion of M2-1ike TAMs or reprogramming them into M l-like pheno- type enhances the efficacy of these therapies （Rolny et al., 2011; de Palma and Lewis, 2013; Germano et al., 2013）. Chemotherapy has been shown to increase macrophage infiltration in human breast cancer tis- sues and the ratio of CD68/CD8 expression predicts the patient response to the treatment （DeNardo et al., 2011）. TAMs have been known to promote breast cancer progression and increase therapy resistance through mechanisms such as the enhancement of angiogenesis, tumor cell proliferation and invasive- ness by producing growth factors such as vascular endothelial growth factor （VEGF）, epidermal growth factor （EGF） and FGF2 （Jiang, 2014）.展开更多
目的分析脑脊液白细胞介素-6(interleukin-6,IL-6)、白细胞介素-10(interleukin-10,IL-10)对原发性眼内淋巴瘤(primary intraocular lymphoma,PIOL)患者预后的预测价值。方法采用回顾性研究方法,选取2018年1月~2022年12月中国医学科学院...目的分析脑脊液白细胞介素-6(interleukin-6,IL-6)、白细胞介素-10(interleukin-10,IL-10)对原发性眼内淋巴瘤(primary intraocular lymphoma,PIOL)患者预后的预测价值。方法采用回顾性研究方法,选取2018年1月~2022年12月中国医学科学院/北京协和医学院北京协和医院收治的60例PIOL患者,出院后随访2年进行预后评估,统计不良预后发生率。将发生不良预后的患者纳入预后不良组,将未发生不良预后的患者纳入预后良好组,对比两组入院时的临床资料。采用多因素Logistic回归分析评价脑脊液IL-6、IL-10对预后的影响。绘制受试者工作特征(receiver operating characteristic,ROC)曲线,分析脑脊液IL-6、IL-10对预后的预测价值。结果60例患者随访2年后,22例出现不良预后,不良预后发生率为36.67%。预后不良组22例,预后良好组38例;2组的脑脊液IL-6、IL-10比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,脑脊液IL-6、IL-10是PIOL患者不良预后的危险因素。脑脊液IL-6、IL-10联合检测对预后预测的曲线下面积(area under the curve,AUC)、敏感度、特异性分别为0.879、85.53%、91.46%,高于脑脊液IL-6、IL-10单项检测。结论脑脊液IL-6、IL-10对PIOL患者预后具有一定的预测价值,高IL-6、IL-10水平提示预后不良。展开更多
基金This work was supported by research funding from the Italian Telethon Foundation(TGT17G01)the Italian Assodation for Cancer Research,IG-18540,AIRC 2016 to S.G.+1 种基金by COST Action BM1305 A-FAACT(http://www.afactt.eu)and COST Action BM1404 Mye EUNITER(http://www.mye euniter.eu)COST is supported by the EU Framework Program Horizon 2020.MJ.U.was supported by the NSF Graduate Research Fellowship Grant#DGE-1147470.
文摘Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting tolerance.DC-10,a tolerogenic population of human IL-10-producing DCs characterized by the expression of HLA-G and ILT4,play a pivotal role in promoting tolerance via T regulatory type 1(Tr1)cells.Thus far,the absence of markers that uniquely identify DC-10 has limited in vivo studies.By in vitro gene expression profiling of differentiated human DCs,we identified CD141 and CD163 as surface markers for DC-10.The coexpression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of DC-10 from the peripheral blood.CD14+CD16+CD141+CD163+cells isolated from the peripheral blood of healthy subjects(ex vivo DC-10)produced spontaneously and upon activation of IL-10 and limited levels of IL-12.Moreover,in vitro stimulation of allogeneic naive CD4+T cells with ex vivo DC-10 induced the differentiation of alloantigen-specific CD49b+LAG-3+Tr1 cells.Finally,ex vivo DC-10 and in vitro generated DC-10 exhibited a similar transcriptional profile,which are characterized by an anti-inflammatory and pro-tolerogenic signature.These results provide new insights into the phenotype and molecular signature of DC-10 and highlight the tolerogenic properties of circulating DC-10.These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.
文摘Macrophages are among the most abundant immune cells in the tumor microenvironment, where they are known as tumor-associated macrophages （TAMs）. Substantial evidence indicates that TAMs generally play pro＇tumoral roles in the primary as well as metastatic sites （Noy and Pollard, 2014）. TAMs are also known to interfere with several tumor therapeutic modalities, such as chemotherapy, irradiation, and immunotherapy. In general, depletion of M2-1ike TAMs or reprogramming them into M l-like pheno- type enhances the efficacy of these therapies （Rolny et al., 2011; de Palma and Lewis, 2013; Germano et al., 2013）. Chemotherapy has been shown to increase macrophage infiltration in human breast cancer tis- sues and the ratio of CD68/CD8 expression predicts the patient response to the treatment （DeNardo et al., 2011）. TAMs have been known to promote breast cancer progression and increase therapy resistance through mechanisms such as the enhancement of angiogenesis, tumor cell proliferation and invasive- ness by producing growth factors such as vascular endothelial growth factor （VEGF）, epidermal growth factor （EGF） and FGF2 （Jiang, 2014）.
文摘目的分析脑脊液白细胞介素-6(interleukin-6,IL-6)、白细胞介素-10(interleukin-10,IL-10)对原发性眼内淋巴瘤(primary intraocular lymphoma,PIOL)患者预后的预测价值。方法采用回顾性研究方法,选取2018年1月~2022年12月中国医学科学院/北京协和医学院北京协和医院收治的60例PIOL患者,出院后随访2年进行预后评估,统计不良预后发生率。将发生不良预后的患者纳入预后不良组,将未发生不良预后的患者纳入预后良好组,对比两组入院时的临床资料。采用多因素Logistic回归分析评价脑脊液IL-6、IL-10对预后的影响。绘制受试者工作特征(receiver operating characteristic,ROC)曲线,分析脑脊液IL-6、IL-10对预后的预测价值。结果60例患者随访2年后,22例出现不良预后,不良预后发生率为36.67%。预后不良组22例,预后良好组38例;2组的脑脊液IL-6、IL-10比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,脑脊液IL-6、IL-10是PIOL患者不良预后的危险因素。脑脊液IL-6、IL-10联合检测对预后预测的曲线下面积(area under the curve,AUC)、敏感度、特异性分别为0.879、85.53%、91.46%,高于脑脊液IL-6、IL-10单项检测。结论脑脊液IL-6、IL-10对PIOL患者预后具有一定的预测价值,高IL-6、IL-10水平提示预后不良。
