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Decoding and targeting the PGE2-MEF2A axis in tumor-associated macrophages

Project description

Tipping the balance in immunotherapy through inflammatory gene control

Pancreatic cancer is an incurable disease, and researchers suspect that this is due to aberrant inflammation sustaining the tumour. One way to improve available treatment tools lies in enhancing cytotoxicity and reducing regeneration that take place during inflammation. With this in mind, the ERC-funde MEFHISTO project will focus on understanding the role of tumour-associated macrophages (TAMs) in orchestrating the balance between these two conflicting processes. The project will combine functional experiments with preclinical models to shed light on a newly described molecular pathway that specifically controls inflammation in TAMs. Through its efforts, MEFHISTO seeks to provide invaluable insights for immunotherapy.

Objective

Inflammation is a complex spectrum of processes whose outcomes range from cell killing to tissue regeneration. In this context, a major goal in immune oncology is the development of treatments that stimulate cytotoxic immunity while limiting repair in the tumor microenvironment (TME), as these approaches have the potential to synergize with available immunotherapies and provide benefit to otherwise resistant patients. Pancreatic cancer is a largely incurable disease, in which aberrant inflammation and profound immune suppression conspire to sustain disease initiation, progression, and immune escape. Accumulating evidence supports the view that tumor-associated macrophages (TAMs) are key orchestrators of the balance between cytotoxicity and regeneration, and thus represent promising therapeutic targets in pancreatic cancer. In MEFHISTO, we aim at elucidating the molecular control, the functional implications, and the therapeutic potential of the PGE2-MEF2A axis, a newly described pathway enabling selective control of inflammatory gene expression in macrophages. By combining advanced genomic analyses in human samples, functional experiments in preclinical models, and mechanistic studies in key cell types, this Proposal will expand our knowledge of the organizing principles of innate immune responses in tumors. The ensuing results may lead to novel combinatorial treatments for diseases, such as pancreatic cancer, that are refractory to immunotherapy.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2022-COG

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Host institution

UNIVERSITA VITA-SALUTE SAN RAFFAELE
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.

€ 936 875,00
Address
VIA OLGETTINA 58
20132 Milano
Italy

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Region
Nord-Ovest Lombardia Milano
Activity type
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.

€ 2 000 000,00

Beneficiaries (2)

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