X-TAM | Dissecting Cross-Regulatory Interplays in Tumor-Associated Macrophages

Summary
Macrophages are specialized innate immune cells with central roles in homeostasis and disease. Upon
exposure to micro-environmental stimuli, these cells can adopt a variety of phenotypes ranging from immune
stimulation and cytotoxicity to immune suppression and tissue repair. Dynamic transitions between these
functional properties in response to tumor signals is thought to underlie the generally pathogenic role of
macrophages in cancer. At the same time, macrophage plasticity could be exploited to therapeutically
reprogram the phenotype of these cells by pharmacological, cell and gene therapy approaches.
Current models of macrophage activation are based on in-depth analyses of the effect of individual stimuli,
such as pro- or anti-inflammatory cytokines, on the biochemical, cell biological, epigenetic, transcriptional
and post-transcriptional landscape of macrophages. However, these studies do not take into consideration the
interplay that these stimuli may have when present at the same time.
This project aims to elucidate how macrophages integrate incoherent environmental stimuli at the genomic
level, and translate them into context-specific gene expression programs. Because concomitant activation of
antagonistic pro-inflammatory and anti-inflammatory pathways is almost invariably observed in cancer, we
propose that these interplays are critical determinants of the biology of tumor-associated macrophages.
Our approach integrates cutting-edge genomics and computational modelling with in vitro functional
screenings and in vivo manipulation of macrophages, building on uniquely available gene therapy platforms.
Successful completion of this project will generate widely exportable paradigms of gene regulation in the
immune system, and deliver innovative cell and gene therapy strategies to manipulate the behaviour of
macrophages in cancer.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/759532
Start date: 01-03-2018
End date: 31-08-2023
Total budget - Public funding: 1 498 125,00 Euro - 1 498 125,00 Euro
Cordis data

Original description

Macrophages are specialized innate immune cells with central roles in homeostasis and disease. Upon
exposure to micro-environmental stimuli, these cells can adopt a variety of phenotypes ranging from immune
stimulation and cytotoxicity to immune suppression and tissue repair. Dynamic transitions between these
functional properties in response to tumor signals is thought to underlie the generally pathogenic role of
macrophages in cancer. At the same time, macrophage plasticity could be exploited to therapeutically
reprogram the phenotype of these cells by pharmacological, cell and gene therapy approaches.
Current models of macrophage activation are based on in-depth analyses of the effect of individual stimuli,
such as pro- or anti-inflammatory cytokines, on the biochemical, cell biological, epigenetic, transcriptional
and post-transcriptional landscape of macrophages. However, these studies do not take into consideration the
interplay that these stimuli may have when present at the same time.
This project aims to elucidate how macrophages integrate incoherent environmental stimuli at the genomic
level, and translate them into context-specific gene expression programs. Because concomitant activation of
antagonistic pro-inflammatory and anti-inflammatory pathways is almost invariably observed in cancer, we
propose that these interplays are critical determinants of the biology of tumor-associated macrophages.
Our approach integrates cutting-edge genomics and computational modelling with in vitro functional
screenings and in vivo manipulation of macrophages, building on uniquely available gene therapy platforms.
Successful completion of this project will generate widely exportable paradigms of gene regulation in the
immune system, and deliver innovative cell and gene therapy strategies to manipulate the behaviour of
macrophages in cancer.

Status

CLOSED

Call topic

ERC-2017-STG

Update Date

27-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.1. EXCELLENT SCIENCE - European Research Council (ERC)
ERC-2017
ERC-2017-STG