Transparent Tumor Tomography (T3): Multi-Parameter 3D Imaging for Tumor Immunotherapy

透明肿瘤断层扫描 (T3)：用于肿瘤免疫治疗的多参数 3D 成像

基本信息

批准号：
9886247
负责人：
Steve Seung-Young Lee
金额：
$ 24.9万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-10 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9886247
关键词：
3-Dimensional Advanced Development Aftercare Antibodies Antibody Response Antibody Therapy Antigens Biological Assay Biopsy Blocking Antibodies Blood Vessels Brain Cancer Biology Cancer Diagnostics Cells Cicatrix Combination immunotherapy Cytometry Development Diagnosis Diagnostic Drug Delivery Systems Evaluation Extravasation Fluorescence Microscopy Human Image Imaging Techniques Immune Immune response Immunofluorescence Immunologic Immunohistochemistry Immunologic Markers Immunologics Immunooncology Immunotherapeutic agent Immunotherapy Inflammatory Infiltrate Intervention Knowledge Label Light Location Lymphocytic Infiltrate Malignant Neoplasms Manuscripts Maps Mediating Methodology Methods Microtomy Modeling Monitor Morphologic artifacts Morphology Mus Neurons Neurosciences Oncologist Optics Organ Outcome Pathologist Patients Pattern Penetration Pharmaceutical Preparations Population Protocols documentation Radiation Radiation therapy Research Residual Tumors Resolution Rodent Sampling Science Selection for Treatments Specimen Stains Stromal Cells Structure Techniques Therapeutic Therapeutic antibodies Thick Three-Dimensional Imaging Time Tissues Tumor Biology Tumor Immunity Tumor Subtype Tumor Tissue Uncertainty anti-tumor immune response antibody immunotherapy base brain tissue cancer cell cancer imaging cancer immunotherapy chemotherapy clinical practice density design drug distribution effective therapy fluorescence imaging high resolution imaging imaging approach imaging modality immune checkpoint improved in vivo in vivo imaging light microscopy neoplasm immunotherapy novel outcome forecast predicting response prevent programmed cell death ligand 1 reconstruction response spatiotemporal three-dimensional visualization tomography tool treatment response tumor tumor growth tumor immunology tumor microenvironment two photon microscopy two-dimensional

项目摘要

Project Summary This proposal aims to apply an imaging technique for three-dimensional (3D) visualization and mapping of the tumor and microenvironment including cancer cells, stromal cells, immune cells, and vascular cells. The capability to determine the location, density, and functional orientation of different cell populations throughout a tumor would be a powerful tool not only for cancer biology but also for improving diagnosis and advancing the development of effective therapies. Although immunohistochemistry (IHC)/immunofluorescence (IF) staining has long been used in cancer diagnostics, conventional IHC/IF methodology is based on localization of antigens in single thin sections. Considering that most cells in the field of view may be only fragments, interpretation of thin section staining is subject to multiple artifacts. Significantly, IHC/IF may fail to demonstrate important features such as pushing margin, lymphocytic infiltrate, or squamous change, leaving room for diagnostic and therapeutic uncertainties. Recent progress in tissue optical clearing and light microscopy enable 3D fluorescent imaging of normally opaque, thick tissues and organs. Dramatic examples include progress mapping neuronal connectivity in whole rodent brains at subcellular resolution. I sought to adapt these strategies to advance analysis of inflammatory infiltrates, drug delivery, and therapeutic responses in whole mouse tumors and human tumor biopsies. In order to advance 3D tumor imaging, I optimized optical clearing, cell staining, high resolution imaging, and computational reconstruction. Eventually, I developed a 3D tumor imaging method, Transparent Tumor Tomography (T3), as a tool to visualize and map tumors at single cell resolution. In this project, I will apply T3 for spatial analysis of tumor immunology and immunotherapy. T3-mediated 3D tumor imaging will provide integrated spatial information regarding antibody drug distribution and immune contexts in whole tumors which will be useful as a new assay tool for cancer immunotherapy research.

项目概要该提案旨在应用成像技术进行三维（3D）可视化和映射肿瘤和微环境，包括癌细胞、基质细胞、免疫细胞和血管细胞。这能够确定整个过程中不同细胞群的位置、密度和功能方向肿瘤不仅将成为癌症生物学的强大工具，而且也将成为改善诊断和推进癌症治疗的强大工具。开发有效的疗法。尽管免疫组织化学 (IHC)/免疫荧光 (IF) 染色长期以来一直用于癌症诊断，传统的 IHC/IF 方法基于定位单个薄片中的抗原。考虑到视野中的大部分细胞可能只是碎片，薄切片染色的解释受到多种伪影的影响。值得注意的是，IHC/IF 可能无法证明重要特征，如推缘、淋巴细胞浸润或鳞状改变，为诊断和治疗的不确定性。组织光学透明和光学显微镜的最新进展使正常情况下的 3D 荧光成像成为可能不透明、厚的组织和器官。戏剧性的例子包括绘制整个神经元连接的进展啮齿动物大脑的亚细胞分辨率。我试图调整这些策略来推进炎症分析整个小鼠肿瘤和人类肿瘤活检中的浸润、药物递送和治疗反应。在为了推进 3D 肿瘤成像，我优化了光学透明、细胞染色、高分辨率成像，以及计算重建。最终，我开发了一种3D肿瘤成像方法，透明肿瘤断层扫描 (T3)，作为一种以单细胞分辨率可视化和绘制肿瘤图谱的工具。在这个项目中，我将应用T3 用于肿瘤免疫学和免疫治疗的空间分析。 T3 介导的 3D 肿瘤成像将提供整合有关整个肿瘤中抗体药物分布和免疫环境的空间信息，将可作为癌症免疫治疗研究的新检测工具。