Identification of a microRNA signature in dendritic cell vaccines for cancer immunotherapy.

Abstract:

: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, CD83, 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.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Holmstrøm K,Pedersen AW,Claesson MH,Zocca MB,Jensen SS

doi

10.1016/j.humimm.2009.10.001

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

67-73

issue

1

eissn

0198-8859

issn

1879-1166

pii

S0198-8859(09)00608-9

journal_volume

71

pub_type

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