Periodic Reporting for period 1 - DRIMMS (Dissecting the role of the immune microenvironment in the onset of myelodysplastic syndromes)
Reporting period: 2023-09-01 to 2025-08-31
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.
In order to characterize immune cells in the bone marrow of both MDS patients and healthy donors, I proposed to perform state-of-the-art analyses that can provide information of the identity and state of single cells within a large cell population, therefore allowing the assessment of both qualitative and quantitative (distribution within the population) features. In the first 4 months of this proposal, I performed a proof-of-principle pilot study in bone marrow cells from 2 healthy donors and successfully set up the technical and analytical details of the experiment, confirming that I can indeed perform a high-throughput analysis in bone marrow specimens and detect sufficient numbers of all major immune cell types with a high-enough resolution to delve deeper into cell subpopulations. I also collected bone marrow plasma samples for a later analysis of the plasma protein landscape of patients and healthy donors.
I expect the progress made in this project to be the starting point for the proposed experiments, which will still be carried out in my laboratory beyond termination of the project. Completion of the project’s aims will significantly advance our understanding of the role of immune evasion in the development of myeloid neoplasms such as MDS and provide novel therapeutic targets for immune reprogramming or immune cell therapy in MDS patients.