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Immunity under Pressure: Mapping Compression Driven Tumor–Immune Rewiring to Potentiate Immunotherapy in Pancreatic Cancer

Objective

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense, stiff stroma and elevated compressive forces within its tumor microenvironment, yet mechanical abnormalities are overlooked in treatment decisions. My prior work has shown that compression reprograms PDAC cells, activating pathways that drive migration and chemotherapy resistance. While chemotherapy remains the standard of care, its toxicity and limited survival benefits highlight the need for alternatives, such as immunotherapies, which harness the immune system but show minimal efficacy in PDAC. My preliminary data indicate that compression drives immune evasion, metabolic rewiring, and an immunosuppressive niche, yet the mechanisms linking compressive stress to immunotherapy failure remain unresolved. MechanoImmunoMap integrates experimental and computational approaches to map how compressive forces reprogram tumor-immune interactions. Bioengineered 3D coculture models of tumor and immune cells under tunable compression, combined with multiomic profiling and mathematical modeling, will identify mechano-immunoregulatory pathways. These pathways will be validated in vivo using mechanically characterized orthotopic PDAC models to build a comprehensive map of compression-driven tumor-immune rewiring. Linking mapped pathways to therapeutic target databases will identify drugs capable of counteracting compression-induced resistance. Prioritized drug candidates will be tested in vitro with immunotherapy and validated in vivo to deliver novel combination therapies that potentiate immunotherapy. Finally, machine learning models will be employed to link compressive stress with multiomic tumor-immune profiling, establishing an engineering framework for immunotherapy response prediction. MechanoImmunoMap transforms compressive forces from a neglected barrier into a biomarker and therapeutic target, laying the foundation for mechanically informed precision oncology in PDAC and other solid tumors.

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Keywords

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Programme(s)

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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-2026-STG

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Host institution

UNIVERSITY OF CYPRUS
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.

€ 1 500 000,00
Address
AVENUE PANEPISTIMIOU 2109 AGLANTZI
1678 Nicosia
Cyprus

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Region
Κύπρος Κύπρος Κύπρος
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.

€ 1 500 000,00

Beneficiaries (1)