Identification of a microRNA signature in dendritic cell vaccines for cancer immunotherapy
Identification of a microRNA signature in dendritic cell vaccines for cancer immunotherapy
复制标题
DOI：
10.1016/j.humimm.2009.10.001
复制
发表时间：
2010-01-01
期刊：
影响因子：
2.7
通讯作者：
Jensen, Simon Skjode
中科院分区：
文献类型：
--
作者：
Holmstrom, Kim;Pedersen, Ayako Wakatsuki;Jensen, Simon Skjode
树突状细胞(DC)暴露于肿瘤抗原，然后用T(H)1极化分化信号处理，为基于DC的肿瘤疫苗的发展铺平了道路。过去，评估DC的最佳功能状态和预测激活DC的疫苗效力的关键参数一直基于对分化表面标志物如HLA-DR、CD80、CID83、CD86和CCR7的测量以及分泌细胞因子如IL-12p70的水平。然而，这些标记物的水平并不能提供DC表型的全貌，可能不足以预测DC治疗的临床结果。因此，我们通过研究成熟DC与未成熟DC中microRNAs(MiRNAs)的差异表达来寻找额外的生物标志物。基于微阵列的筛选显示，12个miRNAs在两种DC表型中差异表达。其中，hsa-miR-155、hsa-miR-146a、hsa-miR-125a-5p和hsa-miR-29a四个miRNAs通过实时定量聚合酶链式反应和Northern杂交得到验证。将12例供者的成熟DC分为高分化DC和低分化DC两组。两组在miRNA诱导水平上有显著差异，这表明对选定的miRNAs的定量评估可能可以预测DC疫苗的免疫原性。(C)2010年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版，版权所有。
Dendritic cells (DCs) exposed to tumor antigens followed by treatment with T(h)1-polarizing differentiation signals have paved the way for the development of DC-based cancer vaccines. Critical parameters for assessment of the optimal functional state of DCs and prediction of the vaccine potency of activated DCs have in the past been based on measurements of differentiation surface markers like HLA-DR, CD80, CID83, CD86, and CCR7 and the level of secreted cytokines like interleukin-12p70. However, the level of these markers does not provide a complete Picture of the DC phenotype and may be insufficient for prediction of clinical outcome for DC-based therapy. We therefore looked for additional biomarkers by investigating the differential expression of microRNAs (miRNAs) in mature DCs relative to immature DCs. A microarray-based screening revealed that 12 miRNAs were differentially expressed in the two DC phenotypes. Of these, four miRNAs, hsa-miR-155, hsa-miR-146a, hsa-miR-125a-5p, and hsa-miR-29a, were validated by real-time polymerase chain reaction and northern blotting. The matured DCs from 12 individual donors were divided into two groups of highly and less differentiated DCs, respectively. A pronounced difference at the level of miRNA induction between these two groups was observed, suggesting that quantitative evaluation of selected miRNAs potentially can predict the immunogenicity of DC vaccines. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.