GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE202916 Query DataSets for GSE202916
Status Public on Nov 09, 2022
Title Targeted erythrophagocyte reprogramming of Kupffer cells halts cancer immunotherapy associated liver toxicity [Multiplexed_CD40]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Agonistic CD40 monoclonal antibodies have emerged as promising immunotherapeutic compounds with impressive anti-tumoral effects. However, one of the main limitations of their use in patients is the severe liver necro-hepatitis they can induce. Up to this point, no effective treatment for anti-CD40 liver toxicity that does not hinder anti-tumor efficacy has been found. In the present study , we show that anti-CD40 liver toxicity is dependent on liver macrophages and recruitment of monocytes and neutrophils. We specifically reprogrammed the phenotype of liver macrophages to anti-inflammatory erythrophagocytes by using repeated injection of anti-erythrocyte murine Ter119 (mTer119) antibody. mTer119 administration induced phagocytosis of erythrocytes by liver macrophages and their transformation to Hmoxhigh/Marcohigh/MHC-IIlow erythrophagocytes. mTer119 treatment prevented anti-CD40 induced liver toxic side-effect, with significantly reduced elevation of plasma transaminases level and area of liver necrosis on histology, while preserving the anti-tumoral efficiency of anti-CD40. Our study offers a novel targeted therapeutic approach to treat immune-related liver adverse side effects of immunotherapies.
Overall design C57BL/6J mice were injected with 20 mg/kg anti-CD40 antibody (InVivoPlus BP0016-2) intraveinously or saline (Control mouse). At 7, 14 or 22 hours post injection, mice were euthanized and their liver digested into a non-parenchymal single-cell suspension. Cells were enriched for leucocytes using CD45+ coated magnetic beads (MagniSort™ Mouse CD45 Positive Selection Kit, 8802-6865-74), stained with Totalseq B hashtag antibodies (Biolegend) and pooled together at equal cell count before processing for single-cell RNA sequencing (Chromium Single Cell 3' Reagent Kits User Guide (v3.1 Chemistry Dual Index) with Feature Barcoding technology for Cell Surface Protein).
Contributor(s) Vallelian F, Pfefferlé M, Dubach I, Schaer DJ
Citation(s) 36593065
Submission date May 12, 2022
Last update date Jan 13, 2023
Contact name Marc Pfefferle
Organization name University hospital Zürich (USZ)
Street address Wagistrasse 12
City Schlieren
State/province Schweiz
ZIP/Postal code 8952
Country Switzerland
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (1)
GSM6138431 Multiplexed CD40 liver experiment
This SubSeries is part of SuperSeries:
GSE202918 Targeted erythrophagocyte reprogramming of Kupffer cells halts cancer immunotherapy associated liver toxicity
BioProject PRJNA837628

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
GSE202916_RAW.tar 103.6 Mb (http)(custom) TAR (of H5AD, MTX, TSV, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap