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Decoding leukemia-immune cell dynamics by organism-wide cellular interaction mapping

Project description

Leukemia-immune cell crosstalk

The immune system has several functions, such as surveillance and defence against foreign pathogens and destruction of damaged or transformed cells. However, cancer cells escape immune detection and control, leading to the development and progression of malignant tumours. Funded by the European Research Council, the InteractOmics project focuses on leukaemia and aims to characterise the dynamic cellular interaction networks between the immune system and cancer cells. Researchers will study how these networks determine anti-cancer immunity and the natural history of disease. Delineation of the mechanisms associated with therapy response and resistance will help predict the outcome of immunotherapies.

Objective

Cellular interactions are of fundamental importance in life, orchestrating organismal development, tissue homeostasis and immunity. In the immune system, cell-cell interactions act as central hubs for information processing and decision making that collectively determine the outcome of complex immune responses. In leukemias, a cancer originating from immature immune cells, a multilayered network of cellular interactions between immune and leukemic cells underlies effective immune control of the cancer, immune evasion and response to immunotherapies. However, technical limitations in studying cell-cell interactions restrict our understanding into these highly complex and dynamic processes. In order to overcome this limitation, I propose to develop a novel interact-omics approach, capable of characterizing millions of cellular interactions across complex organ systems, entire organisms and patient cohorts. Applying the interact-omics approach to sophisticated leukemia mouse models will enable us to dissect the dynamic cellular interaction networks between antigen-specific T cells, bystander immune cells and leukemic cells that drive anti-leukemia immunity and immune evasion. In combination with the in vivo perturbation of cellular interactions, this will allow us to systematically decode the cellular logic of how the complex leukemia-immune interplay determines the disease course. Additionally, by making use of leukemia patient cohorts which are either responsive or non-responsive to immunotherapy treatment, we will unravel previously unknown therapy resistance mechanisms and predict therapy response. Together, our approach will set the basis for a comprehensive understanding of the leukemia-immune cell crosstalk underlying immune control, immune escape and therapy response, and may serve as a blueprint to fundamentally expand our insights into other biological processes driven by cellular interactions.

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HORIZON-ERC - HORIZON ERC Grants

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(opens in new window) ERC-2022-STG

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Host institution

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
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.

€ 1 499 596,00
Address
Chariteplatz 1
10117 Berlin
Germany

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Region
Berlin Berlin Berlin
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.

€ 1 499 596,00

Beneficiaries (1)

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