Role of Follicular Dendritic Cells in B lymphoma

滤泡树突状细胞在 B 淋巴瘤中的作用

• 批准号: 9254489
• 负责人: John R Apgar
• 金额: $ 21.21万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-05 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9254489
• 关键词: Address; Adhesions; Area; B cell differentiation; B lymphoid malignancy; B-Cell Lymphomas; B-Lymphocytes; Biochemical; Blocking Antibodies; Cell Communication; Cell Survival; Cells; Complement; Cytometry; Disease; Elements; Employee Strikes; Event; Extranodal; Follicular Dendritic Cells; Follicular Lymphoma; Future; Gene Expression Profile; Gene Silencing; Human; Image Cytometry; Integrins; Interleukin-6; Investigation; Ligands; Lipids; Liver; Lung; Lymphoid; Lymphoma; Malignant - descriptor; Malignant Neoplasms; Modeling; Molecular Profiling; Mus; Nodal; Organ; Outcome; PTEN gene; Pathway Analysis; Patients; Phosphoric Monoester Hydrolases; Population; Recruitment Activity; Regulation; Research; Role; Sampling; Signal Pathway; Signal Transduction; Signaling Protein; Site; Solid; Solid Neoplasm; Spleen; Stromal Cells; Structure; Supporting Cell; T-Lymphocyte; Therapeutic; Therapeutic Intervention; Tissues; Vascular Cell Adhesion Molecule-1; cell transformation; chemokine; differentiated B cell; experimental study; insight; intercellular cell adhesion molecule; mouse model; public health relevance; receptor; transcriptome; tumor; tumor microenvironment

 DESCRIPTION (provided by applicant): Defining the critical cellular elements of the stroma that support B lymphoma progression at lymphoid and non- lymphoid sites is of great therapeutic potential, yet remains an understudied area of research. The presence of follicular dendritic cells (FDCs) is a hallmark of lymphoid neogenesis in tumors, including B lymphomas. However, the functional importance of the these cells has not been addressed. Herein we will utilize patient- derived follicular lymphoma samples, two murine models of B-NHL, FDC-deficient mice and antibody blocking experiments to determine the contribution of FDC support to B lymphoma formation, progression and dissemination. Lymphoma cells present in lymphoid and neo-lymphoid microenvironments will be further characterized to identify engaged signaling pathways and gene expression signatures to establish profiles of the lymphoma cells, and provide the framework for future studies to investigate the significance and therapeutic potential of particular signaling nodes and microenvironmental factors.

 描述（由申请方提供）：确定支持淋巴和非淋巴部位B淋巴瘤进展的基质关键细胞成分具有巨大的治疗潜力，但仍是一个研究不足的领域。滤泡树突状细胞（follicular dendritic cells，FDCs）的存在是肿瘤（包括B淋巴瘤）中淋巴新生的标志。然而，这些细胞的功能重要性尚未得到解决。在此，我们将利用患者来源的滤泡性淋巴瘤样本、两种B-NHL小鼠模型、FDC缺陷型小鼠和抗体阻断实验来确定FDC支持对B淋巴瘤形成、进展和传播的贡献。淋巴瘤细胞存在于淋巴和新淋巴微环境将进一步确定其特征，以确定参与的信号通路和基因表达特征，以建立淋巴瘤细胞的概况，并为未来的研究提供框架，以研究特定信号节点和微环境因素的意义和治疗潜力。