DRIMMS · Dissecting the role of the immune microenvironment in the onset of myelodysplastic syndromes
„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“
- Период
- 2023-09-01 → 2025-08-31
- Финансиране от ЕС
- 181 153 €
- Участници
- 1
- Схема
- HORIZON-TMA-MSCA-PF-EF
Линиите свързват координатора с партньорите.
Накратко на български
Имунните клетки на пациенти с миелодиспластични синдроми се сравняват със тези на здрави хора, за да се разбере как раковите клетки оцеляват в костния мозък. Това ще помогне при разработването на нови терапии за активиране на защитната реакция на организма.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Dissecting the role of the immune microenvironment in the onset of myelodysplastic syndromes
Myelodysplastic syndromes (MDS) are heterogeneous age-related blood cancers that are incurable by currently approved drugs. The mechanisms that allow tumoral MDS cells to expand and survive in patients’ bone marrows are not fully understood, particularly how patients’ immune systems permit the development of the disease. This information will be key to understand whether new treatment strategies for boosting antitumoral immune responses can be developed. The goal of this project was to characterize MDS patients’ antitumoral immune response by comparing the characteristics of patients’ immune cells with those of healthy individuals’. I proposed to analyze the identity, quantity and functionality of immune cell subsets isolated from patients and age-matched healthy donors as well as their interactions with tumoral cells. I expect my results to reveal immune mechanisms that allow the survival and proliferation of MDS cells and to provide a rationale for the development of novel therapies to eliminate them.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
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.
Оригинален текст от CORDIS (на английски).
Участници
- FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA · PamplonaКоординаторИспания
Връзки
Данни: CORDIS, © Европейски съюз