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Dissecting Cross-Regulatory Interplays in Tumor-Associated Macrophages

Objective

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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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-STG - Starting Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2017-STG

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Host institution

OSPEDALE SAN RAFFAELE SRL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 498 125,00
Address
VIA OLGETTINA 60
20132 Milano
Italy

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Region
Nord-Ovest Lombardia Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 498 125,00

Beneficiaries (1)

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