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Generation and maintenance of long lived memory T cells in humans

Defining the molecular mechanisms governing memory T cell differentiation and homeostasis is of pivotal importance to generate durable and protective T cell responses against infections and cancers. Considerable knowledge in this... ver más

31/05/2021

HUMANITAS MIRASOLE...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

HUMANITAS MIRASOLE SPA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-05-31

ERC-StG-2014: ERC Starting Grant

I+D

Cerrada hace 10 años

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No hay información privada compartida para este proyecto. Habla con el coordinador.

2 Participantes

HUMANITAS MIRASOLE SPA

1.50M€ | Lider

TELEFÓNICA I+D

13.97M€ | Participante

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Duración del proyecto: 71 meses Fecha Inicio: 2015-06-05
Fecha Fin: 2021-05-31

Líder del proyecto

HUMANITAS MIRASOLE SPA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Defining the molecular mechanisms governing memory T cell differentiation and homeostasis is of pivotal importance to generate durable and protective T cell responses against infections and cancers. Considerable knowledge in this regard has been acquired in mouse models but is still limited about human T cells. In particular, some mechanisms are assumed to occur in humans but were never formally demonstrated. We showed that memory T cells adoptively-transferred with bone marrow transplantation failed to persist in recipient hosts in the absence of antigen. By contrast, self/tumor-specific naïve T cells rapidly acquired T memory stem cell (TSCM) attributes and subsequently reconstituted the memory T cell pool by homeostatic differentiation. Current models indicate human TSCM cells as superior to conventional memory T cells in regards to effector potential and persistence capacity. Genome-wide expression analysis identified candidate TSCM cell-specific transcriptional regulators that were shown to inhibit senescence, promote self-renewal and regulate somatic differentiation. In this project, by using single cell technologies, primary human samples and in vivo humanized models, we will define the molecular mechanisms at the basis of memory T cell formation and maintenance in humans. We will initially define the antigenic requirement for the long-term persistence of memory T cells by following the fate of adoptively-transferred T cells. As the field remains unexplored, we will investigate the acquisition of memory attributes by self/tumor-specific T cells on multiple functional levels. The gene products specifically expressed by self-renewing TSCM cells will be finally tested for their capability to arrest T cell differentiation and generate long-lived memory T cells with enhanced stem cell-like properties. Our results will impact multiple physiological and pathological situations involving T cell-mediated immune responses.

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