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Deconstructing the immunomodulatory checkpoints in metastasis to the cerebrospinal fluid

Objective

While the healthy brain is largely devoid of lymphoid cells, the surrounding cerebrospinal fluid (CSF) is normally populated by lymphocytes. CSF hosts an array of threatening pathologies, including leptomeningeal metastasis with unusually poor prognosis. Despite the presence of immune cells, including CD8 T lymphocytes, this metastasis site does not respond to immunotherapy. My preliminary data demonstrate that the molecular profile and phenotypic behavior of these CSF CD8 T cells is inconsistent with conventional immune exhaustion. I hypothesize that CSF is an inherently immunosuppressive environment, protecting the brain from inflammatory insults directly by its composition. In CSFcheck, we will identify the individual components of the CSF that convey its immunosuppressive essence and manipulate the core CD8 T cell gene networks to disrupt the consequences of this phenomenon (Aim 1). We will investigate the fate, lifespan, and function of these cells after the metastasis encounter (Aim 2). Combining my experience with cutting-edge mouse immune modeling, systems-level computation, and functional assessment of human tissues, we will chart the immunosuppressive nature of the CSF and uncover the molecular pressure that CD8 T cells undergo upon entry to the CSF. This work will challenge and refine our understanding of the central nervous system immune privilege and communication with the periphery, exposing novel immunoregulatory mechanisms in metastasis that go beyond T-cell exhaustion.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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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-2025-STG

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Host institution

VIB VZW
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.

€ 1 499 902,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
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.

€ 1 499 902,00

Beneficiaries (1)

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