The role of GM-CSF in the modulation of anti-tumor immunity in myeloproliferative neoplasms.

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Philadelphia-chromosome negative Myeloproliferative neoplasms (MPN) are chronic hematologic diseases and entail essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Although, several preclinical and clinical observations suggest a highly inflammatory microenvironment in these diseases, it remains unclear which cytokine networks dominate in the cell-cell communication and which role they play in the modulation of the TME and the immune response against the malignancy. The type 1 lymphokine GM-CSF represents an important communication conduit between lymphocytes such as T cells and B cells and phagocytes. The aim of this research project is to unravel the dominant cytokine networks in MPN patient samples from bone marrow biopsies and peripheral blood by applying single cell technologies such as high dimensional mass cytometry (HDcyto) and single cell RNA sequencing (scRNAseq) followed by a comprehensive bioinformatic analysis pipeline. In addition, based on the analysis of the human samples the role of the cytokine GM-CSF on the immune environment of MPN will be interrogated and evaluated as a therapeutic target to develop efficient immunotherapies for MPN patients.