NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE221357 Query DataSets for GSE221357
Status Public on Sep 27, 2023
Title In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases [scRNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Liver metastases are associated with poor response to current pharmacological treatments, including immunotherapy. We describe a lentiviral vector (LV) platform to selectively engineer liver macrophages, including Kupffer cells and tumor-associated macrophages (TAMs), to deliver type I interferon (IFNα) to liver metastases. Gene-based IFNα delivery delays the growth of colorectal and pancreatic ductal adenocarcinoma liver metastases in mice. Response to IFNα is associated with TAM immune activation, enhanced MHC-II-restricted antigen presentation and reduced exhaustion of CD8+ T cells. Conversely, increased IL-10 signaling, expansion of Eomes CD4+ T cells, a cell type displaying features of type I regulatory T (Tr1) cells, and CTLA-4 expression are associated with resistance to therapy. Targeting regulatory T cell functions by combinatorial CTLA-4 immune checkpoint blockade and IFNα LV delivery expands tumor-reactive T cells, attaining complete response in most mice. These findings support a promising therapeutic strategy with feasible translation to patients with unmet medical need.
 
Overall design Single-cell transcriptomics on metastatic liver in three distinct cohorts: (1) Control: Control LV-treated mice, (2) Partial responder: IFNa LV-treated mice with reduced tumor volume as compared to Control and, (3) Resistant: IFNa LV-treated mice with tumor volume similar to Control.
 
Contributor(s) Kerzel T, Giacca G, Merelli I, Naldini L, Squadrito ML
Citation(s) 37863068
Submission date Dec 19, 2022
Last update date Jan 04, 2024
Contact name Stefano Beretta
E-mail(s) beretta.stefano1@hsr.it
Organization name San Raffaele Telethon Institute for Gene Therapy
Street address Via Olgettina, 60
City Milan
ZIP/Postal code 20132
Country Italy
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM6859010 Control sample of Tumor liver (Mouse 1)
GSM6859011 Resistant sample of Tumor liver (Mouse 1)
GSM6859012 Control sample of Tumor liver (Mouse 2)
This SubSeries is part of SuperSeries:
GSE221360 In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases
Relations
BioProject PRJNA913955

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
GSE221357_RAW.tar 457.9 Mb (http)(custom) TAR (of MTX, TSV)
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
External link. Please review our privacy policy.