Circulating monocyte subsets with distinct functions play important roles in hepatitis C virus （HCV） infection. However, the mechanisms have not been well studied. In this study, we analyzed the distributions and ph...Circulating monocyte subsets with distinct functions play important roles in hepatitis C virus （HCV） infection. However, the mechanisms have not been well studied. In this study, we analyzed the distributions and phenotypic characteristics of three circulating monocyte subsets--CD14^＋＋CD16^-, CD14^＋＋CD16^＋ and CD14^＋＋mCD16^——in chronic HCV-infected patients, HCV spontaneous resolvers and healthy controls, and we evaluated the possible link between HCV viremia and disease progression. Our results indicated that the frequency of the CD 14^＋＋CD 16^＋ monocyte subset was decreased, and negatively correlated with HCV RNA and core antigen levels during chronic HCV infection. PD-L1 expression and the PD-L1/CD86 ratio in CD14^＋＋CD16^＋ monocytes were higher during chronic HCV infection than in spontaneous HCV resolvers and healthy controls. The PD-L1/CD86 ratio positively correlated with HCV viral load and core antigen levels. Finally, PD-L1 was significantly increased, while cytokine secretions were dramatically decreased upon Toll-like receptor （TLR） ligand binding and HCV JFH-lstimulation. These findings indicates the compromised immune status of the CD14^＋＋CD16^＋ monocytes during chronic HCV infection and provides new insights into the specific role of the CD14^＋＋CD16^＋ monocytes and their significance in chronic HCV infection.展开更多
Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(...Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR CRC.In recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC patients.Preclinical and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in CRC.Herein,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 antibodies.In addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.展开更多
目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)中程序性死亡受体1(programmed death receptor-1,PD-1)及程序性死亡受体配体1(programmed death receptor ligand-1,PD-L1)的表达和EGFR突变及其与预后的关系。方法:收集2013...目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)中程序性死亡受体1(programmed death receptor-1,PD-1)及程序性死亡受体配体1(programmed death receptor ligand-1,PD-L1)的表达和EGFR突变及其与预后的关系。方法:收集2013年01月至2015年12月由我院病理科经组织学诊断为非小细胞肺癌,并完成EGFR突变检测的150例患者的临床资料,应用免疫组织化学方法检测NSCLC组织中PD-1/PD-L1和CD8蛋白表达情况,分析其与临床病理参数及与EGFR突变的相关性,并对影响患者预后的多个临床病理因素进行分析。结果:非小细胞肺癌组织中PD-1/PD-L1和CD8的阳性表达率分别为34.7%(52/150)、50.4%(57/113)和59.2%(84/142)。其中PD-L1的表达与PD-1的表达(P=0.025,r_(s)=0.211)有关;PD-1的表达与术后病理分期(P=0.031,r_(s)=-0.177)及EGFR突变(P=0.001,r_(s)=-0.257)和CD8的表达(P=0.000,r_(s)=0.323)有关;CD8的表达与组织学类型(P=0.048,r_(s)=0.173)有关。对NSCLC患者随访,肿瘤中-低分化程度、临床分期Ⅳ期、存在远处转移及PD-1高表达的患者总生存期分别低于肿瘤高分化程度、临床分期I-III期、不存在远处转移及PD-1低表达的患者(均P<0.05)。结论:PD-1/PD-L1和CD8参与NSCLC的病理过程,PD-1的表达与非小细胞肺癌患者术后病理分期及EGFR突变状态有关,影响患者预后。展开更多
文摘Circulating monocyte subsets with distinct functions play important roles in hepatitis C virus （HCV） infection. However, the mechanisms have not been well studied. In this study, we analyzed the distributions and phenotypic characteristics of three circulating monocyte subsets--CD14^＋＋CD16^-, CD14^＋＋CD16^＋ and CD14^＋＋mCD16^——in chronic HCV-infected patients, HCV spontaneous resolvers and healthy controls, and we evaluated the possible link between HCV viremia and disease progression. Our results indicated that the frequency of the CD 14^＋＋CD 16^＋ monocyte subset was decreased, and negatively correlated with HCV RNA and core antigen levels during chronic HCV infection. PD-L1 expression and the PD-L1/CD86 ratio in CD14^＋＋CD16^＋ monocytes were higher during chronic HCV infection than in spontaneous HCV resolvers and healthy controls. The PD-L1/CD86 ratio positively correlated with HCV viral load and core antigen levels. Finally, PD-L1 was significantly increased, while cytokine secretions were dramatically decreased upon Toll-like receptor （TLR） ligand binding and HCV JFH-lstimulation. These findings indicates the compromised immune status of the CD14^＋＋CD16^＋ monocytes during chronic HCV infection and provides new insights into the specific role of the CD14^＋＋CD16^＋ monocytes and their significance in chronic HCV infection.
基金supported by grants from National Cancer Center Climbing Fund(Grant No.NCC201916B03)Provincial-ministerial Co-construction Project of Henan Province Science and Technology Key Point Tackling Plan(Grant No.SBGJ202102064)Henan Provincial Scientific and Technological Project(Grant Nos.222102310363 and 222102310677)。
文摘Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR CRC.In recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC patients.Preclinical and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in CRC.Herein,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 antibodies.In addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.
文摘目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)中程序性死亡受体1(programmed death receptor-1,PD-1)及程序性死亡受体配体1(programmed death receptor ligand-1,PD-L1)的表达和EGFR突变及其与预后的关系。方法:收集2013年01月至2015年12月由我院病理科经组织学诊断为非小细胞肺癌,并完成EGFR突变检测的150例患者的临床资料,应用免疫组织化学方法检测NSCLC组织中PD-1/PD-L1和CD8蛋白表达情况,分析其与临床病理参数及与EGFR突变的相关性,并对影响患者预后的多个临床病理因素进行分析。结果:非小细胞肺癌组织中PD-1/PD-L1和CD8的阳性表达率分别为34.7%(52/150)、50.4%(57/113)和59.2%(84/142)。其中PD-L1的表达与PD-1的表达(P=0.025,r_(s)=0.211)有关;PD-1的表达与术后病理分期(P=0.031,r_(s)=-0.177)及EGFR突变(P=0.001,r_(s)=-0.257)和CD8的表达(P=0.000,r_(s)=0.323)有关;CD8的表达与组织学类型(P=0.048,r_(s)=0.173)有关。对NSCLC患者随访,肿瘤中-低分化程度、临床分期Ⅳ期、存在远处转移及PD-1高表达的患者总生存期分别低于肿瘤高分化程度、临床分期I-III期、不存在远处转移及PD-1低表达的患者(均P<0.05)。结论:PD-1/PD-L1和CD8参与NSCLC的病理过程,PD-1的表达与非小细胞肺癌患者术后病理分期及EGFR突变状态有关,影响患者预后。
