Objective
Immunotherapies have transformed outcomes across a range of cancers, but not pancreatic ductal adenocarcinoma (PDAC). Recent evidence suggests that PDAC tumors form distinct, context-dependent immunosuppressive niches, but the signals and drivers that control them are still largely enigmatic.
We created unique resources and tools to investigate and target the distinct principles by which PDAC subtypes evade immune destruction, and propose to use them in 3 complementary approaches:
First, we will utilize novel in vivo models reflecting the distinct PDAC immunophenotypes we identified and combine them with novel spatial single-cell barcoding, tracing and perturbation strategies we developed (SpaceMap). This allows us to monitor immunosuppression and -activation dynamics and myeloid (neutrophil and macrophage) mediated cancer cell killing (PhagoQuant) in vivo under basal and therapeutic conditions. These results will lead to the first spatially and temporally resolved atlas of PDAC-immune niche interaction dynamics and function.
Second, we will functionalize the key executors of immunosuppression, neutrophils and macrophages, and perturb their recruitment, retention and polarization into highly immunosuppressive states. These functional studies will uncover the signals that orchestrate distinct myeloid-driven modes of immunosuppression and uncover new ways to reprogram them toward immune activation and cancer cell killing.
Third, we will develop strategies to increase T cell recruitment, persistence and (re)activation, and combine them with myeloid reprogramming and cancer cell targeted therapies, to develop rationale multimodal combinations that evoke durable anti-tumor immunity.
This work will provide fundamental insights into the regulatory principles and dynamic circuits that control the distinct modes of immunosuppression PDAC subtypes utilize to evade immune destruction and will open fundamental new therapeutic horizons for immune-assisted PDAC eradication.
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Keywords
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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
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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.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2025-ADG
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69120 Heidelberg
Germany
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