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immunoMet

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Deciphering immune evasion mechanisms of metastatic cancer cells using CRISPRa-i...

Deciphering immune evasion mechanisms of metastatic cancer cells using CRISPRa-inducible reporters Most cancer patients are resistant to immunotherapies, especially patients with liver and bone metastases. This suggests that during metastasis, cells acquire additional immune evasion mechanisms that dictate susceptibility to imm... ver más

31/08/2026

FORSCHUNGSINSTITUT...

184K€

Presupuesto del proyecto: 184K€

Líder del proyecto

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-13

HORIZON-MSCA-2022-PF-01-01: MSCA Postdoctoral Fellowships 2022 ExpectedOutcome:

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Cerrada hace 2 años

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1 Participantes

FORSCHUNGSINSTITUT FUR MOLEK...

183.60K€ | Lider

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Duración del proyecto: 40 meses Fecha Inicio: 2023-04-13
Fecha Fin: 2026-08-31

Líder del proyecto

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 184K€

Descripción del proyecto Most cancer patients are resistant to immunotherapies, especially patients with liver and bone metastases. This suggests that during metastasis, cells acquire additional immune evasion mechanisms that dictate susceptibility to immunotherapies. Current immunotherapies initiate T cell-mediated killing of cancer cells. However, combining them with agents that target other immune cells in the body, such as natural killer (NK) cells, may be more effective. Whether immune evasion mechanisms of metastatic cells differ between organs and whether these mechanisms can be targeted to improve immunotherapeutic strategies remains unknown. The first aim of this proposal is to leverage a molecular barcoding technique named CaTCH (CRISPRa tracing of clones in heterogenous cell populations) to search for new mechanisms of NK cell immune evasion. CaTCH enables tracing metastatic cancer cells in vivo and isolating clones in a barcode-specific manner for subsequent characterization and functional experiments. We engineered a human non-small-cell lung cancer model with a complex CaTCH barcoding library. Subsequently, we injected the cells into mice harboring NK cells and mice having no NK cells in an experimental metastasis assay. We identified several barcoded clones enriched in specific organs under immune pressure. I aim to investigate this dataset to find novel mechanisms of NK cell immune evasion in the metastatic environment. In the second aim, I will combine molecular barcoding with replicative history tracing of cells to identify cancer clones that evade immune-mediated dormancy in the metastatic niche. I will compare the transcriptional and molecular profiles of dividing cells high in abundance to dividing cells low in abundance to find novel mediators of immune-mediated dormancy. The successful implementation of these aims will uncover new immune evasion strategies of metastatic cells that will pave the way for novel immunotherapeutic strategies for cancer patients.

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