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Series GSE239895 Query DataSets for GSE239895
Status Public on Sep 30, 2023
Title Hiltonol and pRNA stimuli induce an immune activating profile in the transcriptomics of cDC1s [Affy]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Stimulation of dendritic cells (DC) is considered critical in cancer immunotherapy. BATF-3–dependent subsets, that express in humans BDCA-3 (CD141), promote CD8 T-cell cross-priming against tumor antigens. Here, we evaluate two clinical grade stimuli for peripheral blood cDC1 myeloid dendritic cells (mDCs), a rare DC subset that is currently being explored for use in immunotherapy. In contrast to routine evaluation methods, which focus on predefined maturation markers on the surface or factors released from the activated cells, we applied an unbiased transcriptome-based method using both RNA-sequencing (RNA-seq) and microarrays. Specifically, we analyzed the mRNA of cDC1 mDCs from five human donors upon activation with two clinical-grade adjuvants, Hiltonol (poly IC, a TLR3 ligand, called Stimulus 1 in the description below) and protamine RNA (pRNA, aTLR7/8 ligand, Stimulus 2), and compared these samples to unstimulated counterparts. Both methods, RNA-seq and microarray, gave very similar results and showed that Hiltonol and pRNA lead to almost identical changes in the transcriptome of cDC1 mDCs. A gene ontology (GO) term analysis suggested that these changes were mainly related to activation and maturation pathways, including induction of type I IFN and IL-12 transcription, while pathways related to adverse effects or cell damage were not strongly affected. The combination of both reagents in the DC cultures gave a very similar result as compared to either stimulus alone, suggesting no synergistic effect. Together, our results indicate that both stimuli are potent clinical grade adjuvants with comparable effects to mature cDC1 mDCs within an immunogenic profile in short-term cultures suitable to be used in immunotherapy.
Overall design BDCA3 were isolated from blood from 5 donors, 2 treatments were tested separately or in combination (combination not administered to donor 2), an unstimulated control was taken along. Due to limited cell numbers, only microarray analysis was performed for Donor 1.
Contributor(s) Florez-Grau G, Mathan T, Mihaylova MB, van Oorschot T, Buschow SI, Schreibelt G, Reinieren-Beeren I, Sancho D, Melero I, Figdor CG, de Vries I JM, Textor J
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Submission date Aug 02, 2023
Last update date Sep 30, 2023
Contact name Johannes Textor
Organization name Radboud University Medical Center
Street address Geert Groteplein 26-28
City Nijmegen
ZIP/Postal code 6525 GA
Country Netherlands
Platforms (1)
GPL23126 [Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version]
Samples (19)
GSM7676805 Donor 1 unstimulated BDCA3
GSM7676806 Donor 1Hiltonol stimulated BDCA3
GSM7676807 Donor 1 pRNA stimulated BDCA3
This SubSeries is part of SuperSeries:
GSE239899 Hiltonol and pRNA stimuli induce an immune activating profile in the transcriptomics of cDC1s
BioProject PRJNA1001352

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE239895_RAW.tar 431.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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