Defining the role of a newly discovered unconventional T cell subset during myelodysplastic syndrome progression and therapy

Myelodysplastic syndromes (MDS) arise from malignant transformation of the primitive hematopoietic stem cell in the bone marrow (BM).

The only curative therapeutic option for MDS patients is BM transplantation, but its feasibility is hampered by high treatment-related mortality.

The BM is the main site of human hematopoiesis, but how the endogenous immune response is affected during MDS occurrence is unclear.

The definition of the cellular components involved in the immune surveillance against myeloid malignancies is crucial to develop new immunotherapeutic strategies.

We recently reported a new subset of BM-resident innate-like T cells (DNTɑβ) with antitumor capacity in solid cancers in mice (Ponzetta, Cell 2019), but their relevance in the human setting is unknown. Our preliminary data suggest that human DNTɑβ could be involved in the control of myeloid malignancies.

The aim of this study is to provide a comprehensive description of the immune reactions occurring during MDS pathogenesis and to determine whether DNTɑβ could be used as a potential immunotherapeutic tool to treat myeloid malignancies.

We will take advantage of cutting-edge technologies available at KI and through collaborators, allowing our study to be conducted at the highest current technological standards.

Overall, this project will expand the current understanding of the immune response to myeloid malignancies, paving the way to the identification of new immunotherapeutic targets.