γδT cells are a conserved population of innate lymphocytes with diverse structural and functional heterogeneity that participate in various immune responses during tumor progression. γδT cells perform potent immun...γδT cells are a conserved population of innate lymphocytes with diverse structural and functional heterogeneity that participate in various immune responses during tumor progression. γδT cells perform potent immunosurveillance by exerting direct cytotoxicity, strong cytokine production and indirect antitumor immune responses. However, certain γδT-cell subsets also contribute to tumor progression by facilitating cancer-related inflammation and immunosuppression. Here, we review recent observations regarding the antitumor and protumor roles of major structural and functional subsets of human γδT cells, describing how these subsets are activated and polarized, and how these events relate to subsequent function in tumor immunity. These studies provide insights into the manipulation of γδT-cell function to facilitate more targeted approaches for tumor therapy.展开更多
γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of humanγδT cell receptors （TCRs） remain largely unknown, but recent studies ...γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of humanγδT cell receptors （TCRs） remain largely unknown, but recent studies have confirmed the recognition of phosphorylated prenyl metabolites, lipids in complex with CD1 molecules and markers of cellular stress. All of these molecules are upregulated on various cancer types, highlighting the potential importance of the γδ T cell compartment in cancer immunosurveiliance and paving the way for the use of γδTCRs in cancer therapy. Ligand recognition by the γδ TCR often requires accessorylco-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. Unlike αβ T cells, γδ T cells recognise their targets irrespective of HLA haplotype and therefore offer exciting possibilities for off-the-shelf, pan-population cancer immunotherapies. Here, we present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment.展开更多
目的:研究甘草多糖(Glycyrrhizae Radix et Rhizoma polysaccharide,GP)对人外周血γδT细胞增殖、分泌细胞因子、杀伤肿瘤细胞的免疫调节作用。方法:采集正常人静脉抗凝血,加入淋巴细胞分离液,密度梯度离心法分离人单核细胞层,经IPP扩...目的:研究甘草多糖(Glycyrrhizae Radix et Rhizoma polysaccharide,GP)对人外周血γδT细胞增殖、分泌细胞因子、杀伤肿瘤细胞的免疫调节作用。方法:采集正常人静脉抗凝血,加入淋巴细胞分离液,密度梯度离心法分离人单核细胞层,经IPP扩增后得到γδT细胞,采用不同质量浓度的甘草多糖(终质量浓度分别为25,50,100 mg.L-1)。CCK-8法检测甘草多糖对γδT细胞增殖的影响,ELISA法检测甘草多糖对γδT细胞分泌干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)的影响,CCK-8法检测甘草多糖对γδT细胞杀伤功能的影响。结果:甘草多糖能促进γδT细胞增殖,呈剂量依赖关系;甘草多糖作用后,γδT细胞分泌的IFN-γ和TNF-α明显增多(P<0.01),且呈剂量依赖关系;甘草多糖作用后,γδT细胞对肿瘤细胞HepG2的杀伤能力明显增强(P<0.05)。结论:甘草多糖能够促进人外周血γδT细胞增殖、分泌细胞因子及杀伤肿瘤细胞,这为研究甘草多糖的抗肿瘤及免疫调节机制提供了新的依据。展开更多
γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the...γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues, γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and fiver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.展开更多
文摘γδT cells are a conserved population of innate lymphocytes with diverse structural and functional heterogeneity that participate in various immune responses during tumor progression. γδT cells perform potent immunosurveillance by exerting direct cytotoxicity, strong cytokine production and indirect antitumor immune responses. However, certain γδT-cell subsets also contribute to tumor progression by facilitating cancer-related inflammation and immunosuppression. Here, we review recent observations regarding the antitumor and protumor roles of major structural and functional subsets of human γδT cells, describing how these subsets are activated and polarized, and how these events relate to subsequent function in tumor immunity. These studies provide insights into the manipulation of γδT-cell function to facilitate more targeted approaches for tumor therapy.
文摘γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of humanγδT cell receptors （TCRs） remain largely unknown, but recent studies have confirmed the recognition of phosphorylated prenyl metabolites, lipids in complex with CD1 molecules and markers of cellular stress. All of these molecules are upregulated on various cancer types, highlighting the potential importance of the γδ T cell compartment in cancer immunosurveiliance and paving the way for the use of γδTCRs in cancer therapy. Ligand recognition by the γδ TCR often requires accessorylco-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. Unlike αβ T cells, γδ T cells recognise their targets irrespective of HLA haplotype and therefore offer exciting possibilities for off-the-shelf, pan-population cancer immunotherapies. Here, we present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment.
基金This work was supported by the Anhui Natural Science Foundation （No. 1708085QH183）, Natural Science Foundation of China （Nos. 81302863, 31390433, and 91542000）, and the Ministry of Science and Technology of China （973 Program, No. 2013CB944902）.
文摘γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues, γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and fiver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.
