DRIMMS
Financiado
Dissecting the role of the immune microenvironment in the onset of myelodysplastic syndromes
Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic stem-cell malignancies of the elderly. MDS remain uncurable by existing pharmacological therapies, aimed at eradicating mutant clones. Clonal cytopenias of und...
Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic stem-cell malignancies of the elderly. MDS remain uncurable by existing pharmacological therapies, aimed at eradicating mutant clones. Clonal cytopenias of undetermined significance (CCUS) occur in elderly patients harboring MDS-driver mutations in their bone marrow cells and almost always preclude MDS, representing an optimal setting for studying the mechanisms driving the onset of MDS. In a preliminary study, I discovered that innate immune cells from patients with CCUS are transcriptionally rewired toward their activation but have signs of functional exhaustion and dysfunction. Therefore, I hypothesized that dysfunctions in the immune microenvironment favor clonal expansion and disease progression in early stages of MDS and, therefore, therapeutic approaches enhancing the immune response in CCUS or MDS patients may effectively prevent or arrest disease onset. To test my hypothesis, in this project I will dissect the role of the immune microenvironment in the expansion of premalignant clones in early-stage MDS. To do so, I will 1) transcriptionally and immunophenotypically characterize the immune microenvironment in MDS patients with low clonal burden at the single-cell level, including interactions between immune and non-immune cells; 2) assess the functionality of the immune cell repertoire in CCUS and MDS patients through the analysis of their secretome and the cells’ secretory and cytolytic functions; and 3) test the feasibility of targeting immune responses in MDS by performing proof-of-principle drug testing assays with new-generation immune checkpoint inhibitors and identifying and validating novel therapeutic targets. I expect the results of this project to shed light on the cell-extrinsic mechanisms eliciting MDS pathogenesis and provide a biologic rationale for the development of pharmacologic or cellular therapies to prevent or early-treat MDS before outcomes become dismal.
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Duración del proyecto: 28 meses
Fecha Inicio: 2023-04-12
Fecha Fin: 2025-08-31
Fecha Fin: 2025-08-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-12
HORIZON EUROPE
No se conoce la línea exacta de financiación, pero conocemos el organismo encargado de la revisión del proyecto.
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FUNOACION PARA LA INVESTIG
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