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

GM-CSF 在骨髓增殖性肿瘤抗肿瘤免疫调节中的作用。

• 批准号: 463384799
• 负责人: Dr. Tobias Wertheimer
• 金额: --
• 依托单位: Institut für Experimentelle Immunologie
• 依托单位国家: 德国
• 项目类别: WBP Fellowship
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/463384799?language=en
• 关键词: role; GM; CSF; modulation; anti

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.

费城染色体阴性骨髓增生性肿瘤 (MPN) 是一种慢性血液系统疾病，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，但仍不清楚哪些细胞因子网络在细胞间通讯中占主导地位，以及它们在调节 TME 和针对恶性肿瘤的免疫反应中发挥什么作用。 1 型淋巴因子 GM-CSF 代表 T 细胞和 B 细胞等淋巴细胞与吞噬细胞之间的重要通讯管道。该研究项目的目的是通过应用高维质谱流式细胞仪 (HDcyto) 和单细胞 RNA 测序 (scRNAseq) 等单细胞技术，然后采用全面的生物信息学分析流程，揭示来自骨髓活检和外周血的 MPN 患者样本中的主要细胞因子网络。此外，根据对人类样本的分析，将探讨和评估细胞因子 GM-CSF 对 MPN 免疫环境的作用，并将其作为治疗靶点进行评估，为 MPN 患者开发有效的免疫疗法。