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Early expression of stem cell-associated genes within the CD8 compartment after treatment with a tumor vaccine

机译:肿瘤疫苗治疗后,CD8区室内的干细胞相关基因的早期表达

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Using a mouse neuroblastoma cell line, we have demonstrated that vaccination of tumor-free mice with a cell-based vaccine leads to productive immunity and resistance to tumor challenge, while vaccination of tumor-bearing mice does not. The T cell immunity induced by this vaccine, as measured by in vitro assays, is amplified by the depletion of Treg. Our goal is to understand this barrier to the development of protective cellular immunity. mRNA microarray analyses of CD8 + T cells from na?ve or tumor-bearing mice undergoing vaccination were carried out with or without administering anti-CD25 antibody. Gene-expression pathway analysis revealed the presence of CD8 + T cells expressing stem cell-associated genes early after induction of productive anti-tumor immunity in tumor-free mice, prior to any phenotypic changes, but not in tumor-bearing mice. These data demonstrate that early after the induction of productive immune response, cells within the CD8 + T cell compartment adopt a stem cell-related genetic phenotype that correlates with increased anti-tumor function.
机译:使用小鼠神经母细胞瘤细胞系,我们已经证明,用基于细胞的疫苗对无瘤小鼠进行疫苗接种可产生生产性免疫力和对肿瘤激发的抵抗力,而对荷瘤小鼠则不会。通过体外试验测定,由该疫苗诱导的T细胞免疫力通过Treg的耗尽而扩增。我们的目标是了解保护性细胞免疫发展的这一障碍。在接种或未接种抗CD25抗体的情况下,对来自初生或荷瘤小鼠的CD8 + T细胞的mRNA微阵列分析。基因表达途径分析揭示了在无表型小鼠中诱导生产性抗肿瘤免疫后,任何表型改变之前早期表达干细胞相关基因的CD8 + T细胞的存在,但在荷瘤小鼠中则没有。这些数据表明,在诱导生产性免疫应答后的早期,CD8 + T细胞区室中的细胞采用了与干细胞相关的遗传表型,该表型与增加的抗肿瘤功能相关。

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