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REWIRE

Financiado

Rewire the lymph node niche to instruct T cell immunity

Lymph nodes (LN) are communication centers within the lymphatic network that instruct T cell priming and differentiation in homeostasis and disease. Multiple layers of control are achieved by a complex network of signals from stro... ver más

31/12/2028

CEMM FORSCHUNGSZE...

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

CEMM FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZ... 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 2023-10-30

ERC-2023-STG: ERC STARTING GRANTS Scope:Objectives

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1 Participantes

CEMM FORSCHUNGSZENTRUM FUER...

1.50M€ | Lider

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Duración del proyecto: 62 meses Fecha Inicio: 2023-10-30
Fecha Fin: 2028-12-31

Líder del proyecto

CEMM FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZ... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Descripción del proyecto Lymph nodes (LN) are communication centers within the lymphatic network that instruct T cell priming and differentiation in homeostasis and disease. Multiple layers of control are achieved by a complex network of signals from stromal and immune cell compartments. As a result, spatially segregated LN niches coexist that foster diverse T cell lineages. In the context of cancer, T cell differentiation is pushed towards the lineage of exhaustion, with a progenitor exhausted T cell population arising in the LN. Hence, LN are central anatomic sites where T cell exhaustion can be controlled and reversed to eliminate cancer. The key question of REWIRE is: What microenvironmental factors determine the differentiation and maintenance of progenitor exhausted T cells in the LN? Tumor-derived signals reprogram stromal and immune cells within tumor-draining LN. Thus, a premetastatic niche is formed that supports future metastatic seeding while establishing an immunosuppressive microenvironment. I hypothesize that signals guiding T cell differentiation are altered by premetastatic remodeling of the LN niche, resulting in the generation of exhausted T cells. In this project, I aim to (1) decode spatial determinants of the progenitor exhausted T cell niche; and to (2) manipulate the tumor-draining LN ecosystem to control T cell immunity. The overarching goal is to dissect how tissue architecture directs molecular responses within the LN niche to regulate T cell exhaustion. We will use high-dimensional imaging technologies to chart the spatial context of progenitor exhausted T cells following tumor progression; as well as a novel myeloid cell-based in vivo delivery platform to specifically target tumor-draining LN. REWIRE will uncover basic mechanisms of communication between the LN microenvironment and differentiating T cells in the LN; as well as explore the novel concept of controlling T cell responses via manipulating key-features of the LN niche.

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