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

费城-染色体阴性骨髓增生性肿瘤(MPN)是一种慢性血液病，会导致原发性血小板增多症(ET)、真性红细胞增多症(PV)和原发性骨髓纤维化(PMF)。尽管一些临床前和临床观察表明，这些疾病存在高度炎症的微环境，但目前尚不清楚哪些细胞因子网络在细胞间通讯中起主导作用，以及它们在调节TME和抗肿瘤免疫反应中发挥什么作用。1型淋巴因子GM-CSF是T细胞、B细胞等淋巴细胞与吞噬细胞之间的重要沟通通道。本研究项目的目的是通过应用单细胞技术，如高维质量细胞术(HDcyto)和单细胞RNA测序(ScRNAseq)，以及随后的综合生物信息学分析流程，从骨髓活检组织和外周血中解开MPN患者样本中的主导细胞因子网络。此外，基于对人体样本的分析，将探讨细胞因子GM-CSF对MPN免疫环境的作用，并将其作为治疗靶点，为MPN患者开发有效的免疫疗法。

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.