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Series GSE202917 Query DataSets for GSE202917
Status Public on Nov 09, 2022
Title Targeted erythrophagocyte reprogramming of Kupffer cells halts cancer immunotherapy associated liver toxicity [Ter119 experiment]
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 A C57BL/6J mouse was injected with a single injection of murine Ter119 antibody subcutaneously (35 ug) followed by 10 daily injections at lower dose (10 ug). Another C57BL/6J mouse was injected with similar volume of saline solution. At 24 after the last injection, mice were euthanized and their liver digested into a non-parenchymal single-cell suspension. Cells were enriched for macofphages using a mixture of anti-F4/80 and anti-CD11b coated magnetic beads (Anti-Rat IgG Dynabeads), 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)).
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 (2)
GSM6138432 Ter119 experiment: Control
GSM6138433 Ter119 experiment: Ter119
This SubSeries is part of SuperSeries:
GSE202918 Targeted erythrophagocyte reprogramming of Kupffer cells halts cancer immunotherapy associated liver toxicity
BioProject PRJNA837627

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Supplementary file Size Download File type/resource
GSE202917_RAW.tar 208.8 Mb (http)(custom) TAR (of MTX, TSV)
GSE202917_Ter_vs_Ctrl_F480_cd11b.h5ad.gz 247.5 Mb (ftp)(http) H5AD
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Processed data are available on Series record

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