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

Summary
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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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101088887
Start date: 01-09-2023
End date: 31-08-2028
Total budget - Public funding: 2 000 000,00 Euro - 2 000 000,00 Euro
Cordis data

Original description

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.

Status

SIGNED

Call topic

ERC-2022-COG

Update Date

31-07-2023
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2022-COG ERC CONSOLIDATOR GRANTS
HORIZON.1.1.1 Frontier science
ERC-2022-COG ERC CONSOLIDATOR GRANTS