Academic Journal
Harnessing RNA sequencing for global, unbiased evaluation of two new adjuvants for dendritic-cell immunotherapy
| العنوان: | Harnessing RNA sequencing for global, unbiased evaluation of two new adjuvants for dendritic-cell immunotherapy |
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| المؤلفون: | Mathan, T.S.M. (Till S.M.), Textor, J. (Johannes), Sköld, A.E. (Annette E.), Reinieren-Beeren, I. (Inge), van Oorschot, T. (Tom), Brüning, M. (Mareke), Figdor, C.G. (Carl), Buschow, S.I. (Sonja I.), Bakdash, G. (Ghaith), Vries, I.J.M. (Jolanda) de |
| المصدر: | Oncotarget vol. 8 no. 12, pp. 19879-19893 |
| سنة النشر: | 2017 |
| المجموعة: | RePub - Publications from Erasmus University, Rotterdam |
| مصطلحات موضوعية: | Adjuvants, Dendritic cells, Immunotherapy, Protamine-RNA, RNA sequencing, Transcriptomics |
| الوصف: | 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. GMCSF 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 clinicalgrade 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | http://repub.eur.nl/pub/98916; urn:hdl:1765/98916 |
| DOI: | 10.18632/oncotarget.15190 |
| الاتاحة: | http://repub.eur.nl/pub/98916 https://doi.org/10.18632/oncotarget.15190 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6E0A8FE |
| قاعدة البيانات: | BASE |
| DOI: | 10.18632/oncotarget.15190 |
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