Elucidating the Role of Neuropilin-1 in Intratumoral Regualtory T Cell Stability

阐明 Neuropilin-1 在瘤内调节性 T 细胞稳定性中的作用

基本信息

批准号：
9070295
负责人：
Abigail E Overacre-Delgoffe
金额：
$ 4.36万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2017-08-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9070295
关键词：
Address Affect Anti-Inflammatory Agents Anti-inflammatory Autoimmune Diseases Autoimmunity Binding Biochemistry Biological Cancer Biology Cancer Patient Cell Nucleus Cell physiology Cells Chronic Data Environment Equilibrium Exhibits Fatty acid glycerol esters Flow Cytometry Genes Genetic Genotype Goals Heterozygote IFNGR1 gene Immune response Immune system Immunity Immunoblotting Immunologic Techniques Immunotherapy Infection Inflammatory Interferon Type II Lead Ligand Binding Ligands Ligation Malignant Neoplasms Mediating Mediator of activation protein Methylation Modeling Molecular Mus Neuropilin-1 Pathway interactions Phenocopy Phenotype Play Population Proto-Oncogene Proteins c-akt Regulatory T-Lymphocyte Research Research Proposals Resistance Role Rosa Semaphorins Signal Transduction Surface System T-Lymphocyte Tissues Training Tumor Immunity X Chromosome X Inactivation base cancer immunotherapy career cytokine gain of function melanoma mouse model outcome forecast pathogen prevent public health relevance receptor research study response transcription factor tumor tumor growth tumor immunology tumor microenvironment

项目摘要

DESCRIPTION (provided by applicant): The adaptive immune system serves to eliminate pathogens while sparing host tissue. The efficiency of this system is largely dependent on balance; unrestrained immunity can cause autoimmunity while a slow or absent response can lead to chronic infection and cancer. Regulatory T cells (Tregs) play a critical role in maintainin this balance through the suppression of self-reactive immune responses. Treg stability is crucial to maintain effective suppressive capacity. Neuropilin-1 (Nrp1), a surface receptor has emerged as an important mediator of Treg stability. Nrp1 binds the ligand, Semaphorin-4a (Sema-4a), leading to enhanced Treg stability intratumorally. In the absence of Nrp1:Sema4a ligation, Tregs lose stability and suppressive capabilities, leading to enhanced anti-tumor immunity and reduced tumor growth. The fate and function of Nrp1-deficient Tregs is unclear. This research proposal suggests experiments that will propel our understanding of how Nrp1 alters Treg stability, and will elucidate the molecular mechanisms leading to a distinct Treg cell population and reduced tumor growth. Understanding these mechanisms is of crucial importance in understanding tumor immunology, and in creating new targets for immunotherapy.

描述（由申请人提供）：适应性免疫系统用于消除病原体，同时保护宿主组织，该系统的效率很大程度上取决于平衡；不受限制的免疫可能导致自身免疫，而缓慢或缺乏反应可能导致慢性感染和癌症。调节性 T 细胞 (Treg) 通过抑制自身反应性免疫反应在维持这种平衡方面发挥着关键作用，Treg 的稳定性对于维持有效的抑制能力至关重要。 Nrp1 已成为 Treg 稳定性的重要调节剂，与配体 Semaphorin-4a (Sema-4a) 结合，导致肿瘤内 Treg 稳定性增强。 Nrp1 缺陷的 Tregs 的命运和功能尚不清楚，这项研究建议进行实验，以促进我们对 Nrp1 如何改变的理解。 Treg 稳定性，并将阐明导致独特 Treg 细胞群和减少肿瘤生长的分子机制，了解这些机制对于理解肿瘤免疫学和创建免疫治疗新靶标至关重要。