Abstract |
Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing ( RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC- vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine- RNA complexes (pRNA) and CpG-P. We found that GM-CSF and pRNA had similar effects on their target cells, whereas pRNA and CpG-P induced stronger type I interferon (IFN) expression than FSME. In general, the pathways most affected by all stimuli were related to immune activity and cell migration. GM-CSF stimulation, however, also induced a significant increase of genes related to nonsense-mediated decay, indicating a possible deleterious effect of this stimulus. Taken together, the two novel stimuli appear to be promising alternatives. Our study demonstrates how RNA-seq based investigation of changes in a large number of genes and gene groups can be exploited for fast and unbiased, global evaluation of clinical-grade stimuli, as opposed to the general limited evaluation of a pre-specified set of genes, by which one might miss important biological effects that are detrimental for vaccine efficacy.
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Authors | Till S M Mathan, Johannes Textor, Annette E Sköld, Inge Reinieren-Beeren, Tom van Oorschot, Mareke Brüning, Carl G Figdor, Sonja I Buschow, Ghaith Bakdash, I Jolanda M de Vries |
Journal | Oncotarget
(Oncotarget)
Vol. 8
Issue 12
Pg. 19879-19893
(Mar 21 2017)
ISSN: 1949-2553 [Electronic] United States |
PMID | 28186996
(Publication Type: Journal Article)
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Chemical References |
- Adjuvants, Immunologic
- Antigens, CD1
- CD1C protein, human
- CPG-oligonucleotide
- FSME-IMMUN vaccine
- Glycoproteins
- Interferon Type I
- Oligodeoxyribonucleotides
- Protamines
- Vaccines
- Viral Vaccines
- RNA
- Granulocyte-Macrophage Colony-Stimulating Factor
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Topics |
- Adjuvants, Immunologic
(pharmacology)
- Antigens, CD1
(immunology, metabolism)
- Cells, Cultured
- Cluster Analysis
- Dendritic Cells
(drug effects, immunology, metabolism)
- Flow Cytometry
- Gene Expression Profiling
(methods)
- Gene Ontology
- Glycoproteins
(immunology, metabolism)
- Granulocyte-Macrophage Colony-Stimulating Factor
(immunology, pharmacology)
- Humans
- Immunotherapy
(methods)
- Interferon Type I
(biosynthesis, genetics, immunology)
- Oligodeoxyribonucleotides
(immunology, pharmacology)
- Protamines
(immunology, pharmacology)
- RNA
(immunology, pharmacology)
- Sequence Analysis, RNA
(methods)
- Transcriptome
(drug effects, immunology)
- Vaccines
(immunology, therapeutic use)
- Viral Vaccines
(immunology, pharmacology)
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