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Dynamic Spatiotemporal Analysis of Immune Cells in the Tumor Microenvironment

肿瘤微环境中免疫细胞的动态时空分析

基本信息

批准号：
10251841
负责人：
Oriana Perez
金额：
$ 3.06万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251841
关键词：
3-Dimensional Anatomy Antitumor Response Atlases Behavior Breast Cancer Model CD8-Positive T-Lymphocytes Cause of Death Cell Adhesion Molecules Cell Communication Cells Colorectal Cancer Complex Cytotoxic T-Lymphocytes Dendritic Cells Detection Development Disease Environment Extracellular Matrix Geography Histologic Hyperplasia Image Imaging Techniques Immune Immunologic Surveillance Immunologics Immunology Immunosuppression Immunotherapeutic agent Immunotherapy In Situ Inflammatory Integrins Leucocytic infiltrate Light Longitudinal Studies Lung Neoplasms Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Measures Mediating Metastatic to Organ Phenotype Play Positioning Attribute Process Production Property Proteins Role Stromal Cells Structure T-Lymphocyte Techniques Technology Testing Time Tissues Tumor stage Tumor-associated macrophages Tumor-infiltrating immune cells Universities Visualization cancer imaging cancer immunotherapy cancer therapy cell motility chemokine chemokine receptor clinically relevant cytokine draining lymph node imaging approach in vivo indexing insight melanoma mouse model multidimensional data multiplexed imaging neoplastic cell new therapeutic target novel novel imaging technique novel strategies outcome forecast patient response prognostic tool receptor recruit response spatiotemporal success treatment strategy tumor tumor eradication tumor growth tumor microenvironment tumor progression tumor-immune system interactions two photon microscopy

项目摘要

Abstract In our study, `Dynamic Spatiotemporal Analysis of Immune Cells in the Tumor Environment' we propose to systemically characterize the spatiotemporal dynamics of immune cells in the tumor microenvironment using a novel imaging technique developed by our collaborators at Stanford University. This technique enables the acquisition of multi-dimensional data by high-throughput visualization of 20-plus proteins from a single tumor section (CO-Detection by indexing). Using this comprehensive imaging approach we will longitudinally study how the organization of immune cells, including tumor-associated macrophages, dendritic cells, and T cells changes over the course of lung tumor development; specifically, by characterizing the dynamics of immune cell remodeling, analyzing expression of activation/suppressive receptors, chemokine receptors and cytokine production. The fundamental principles of immunology have taught us that the organization of immune cells within the tissue is fundamental to their function. Thus, in this proposal we will test the hypothesis that over the course of tumor growth the immunosuppressive tumor microenvironment abrogates the directed reorganization, cell-to-cell interactions and communication of immune cells, necessary for the eradication of tumor cells. These studies will shed important new light on how the immunouppressive tumor microenvironment alters the cellular mechanism that regulate geographical orientation and motile behavior of immune cells and findings from our study will ultimately aid us in identifying new effective targets for cancer immunotherapy.

摘要在我们的研究中，“肿瘤环境中免疫细胞的动态时空分析”，我们建议系统地表征免疫细胞在肿瘤微环境中的时空动态，这是我们在斯坦福大学的合作者开发的一种新的成像技术。该技术使通过高通量可视化单个肿瘤的20多种蛋白质来获取多维数据部分（通过索引进行CO检测）。使用这种全面的成像方法，我们将纵向研究免疫细胞的组织，包括肿瘤相关的巨噬细胞，树突细胞和T细胞，在肺肿瘤发展过程中的变化;特别是，通过表征免疫系统的动态变化，细胞重塑，分析活化/抑制受体、趋化因子受体和细胞因子的表达生产免疫学的基本原理告诉我们免疫细胞的组织对它们的功能至关重要因此，在本提案中，我们将检验以下假设：在肿瘤生长过程中，免疫抑制性肿瘤微环境消除了定向的免疫抑制作用。重组，细胞与细胞的相互作用和免疫细胞的通讯，必要的根除肿瘤细胞这些研究将为免疫抑制性肿瘤微环境改变了调节地理定位和运动行为的细胞机制，免疫细胞和我们的研究结果将最终帮助我们确定癌症的新有效靶点免疫疗法。