Innovating Works

REACT-DC

Financiado
Breaking oncometabolites dynamics for next-generation dendritic cells tumor immu...
"Owing to an increased appreciation of the potential for immunotherapy in neoplasia, much attention has been focuing on a greater understanding of the immune, bidirectional intricacies involving the Tumor MicroEnvironment (TME). R... "Owing to an increased appreciation of the potential for immunotherapy in neoplasia, much attention has been focuing on a greater understanding of the immune, bidirectional intricacies involving the Tumor MicroEnvironment (TME). Recent work has demonstrated that TME elicits environmental changes, metabolic in nature, in the host’s immune cells, that dampen their ability to REACT against tumors. Manipulating the biology of oncometabolites can strengthen an antitumor immune response as well as circumvent therapy resistance. Here I propose innovative modalities to tackle this problem. The Aryl hydrocarbon Receptor (AhR), best known as the receptor for dioxins, has recently been shown to be one ""central node"" for communication between host's cells and its ligands, disparate as the nature and source. I have recently found that selective AhR deletion in a subset of antigen presenting cells triggers the rejection of an otherwise progressive fibrosarcoma tumor in vivo. I thus hypothesize that, AhR, expressed in orchestrators of immune responsiveness, represents a key sensor of TME composition, influencing the outcome of an immune reaction against tumors. The main objective of this project is to identify AhR-activating metabolites in TME and disclose their impact on tumor rejection or progression. In parallel, I aim at developing novel advanced strategies, with a high degree of translatability to human cells, to specifically inhibit AhR or AhR-dependent programs in selected APCs. I will combine state-of-the-art technology with new and powerful technologies, including advanced single-cell analysis, promoter gene-editing approaches and computational chemistry. The potential of such a project is very high, because such metabolites may be predictors of immune activation or suppression in TME, and the downstream targets of those immunesuppressive oncometabiltes may represent druggable targets to inhibit tumor escape mechanisms." ver más
30/06/2028
UNIPG
2M€
Perfil tecnológico estimado
Duración del proyecto: 64 meses Fecha Inicio: 2023-02-07
Fecha Fin: 2028-06-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-02-07
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2022-STG: ERC STARTING GRANTS
Cerrada hace 2 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
UNIVERSITA DEGLI STUDI DI PERUGIA No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5