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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：
9751626
负责人：
Oriana Perez
金额：
$ 6.12万
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/9751626
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 Analysis Imagery Imaging Techniques Immune Immunologic Monitoring Immunologics Immunology Immunosuppression Immunosuppressive Agents 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 cancer imaging cancer immunotherapy cancer therapy cell motility chemokine chemokine receptor clinically relevant cytokine imaging approach in vivo indexing insight lymph nodes 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 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肿瘤微环境中免疫细胞的时空动态我们在斯坦福大学的合作者开发了新的成像技术。这项技术使通过高通量可视化来自单个肿瘤的20多个蛋白质来获取多维数据部分(通过索引进行一氧化碳检测)。使用这种综合的成像方法，我们将纵向研究免疫细胞，包括肿瘤相关巨噬细胞、树突状细胞和T细胞的组织是如何在肺肿瘤发展过程中的变化；具体地说，通过表征免疫动力学细胞重塑，分析激活/抑制受体、趋化因子受体和细胞因子的表达制作。免疫学的基本原理告诉我们，免疫细胞的组织在组织内是它们功能的基础。因此，在本提案中，我们将检验假设肿瘤生长过程中免疫抑制的肿瘤微环境导向免疫细胞的重组、细胞与细胞间的相互作用和交流，对于根除疟疾是必要的肿瘤细胞。这些研究将为免疫抑制肿瘤如何微环境改变细胞机制，调节地理方向和运动行为免疫细胞和我们的研究结果最终将帮助我们确定新的有效抗癌靶点免疫疗法。