Center for Multiparametric Imaging of Tumor Immune Microenvironments

肿瘤免疫微环境多参数成像中心

基本信息

批准号：
10374450
负责人：
Kevin William Eliceiri
金额：
$ 130.91万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-12-09 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10374450
关键词：
Address Advanced Malignant Neoplasm Behavior Biological Models Cancer Biology Cancer Patient Cell physiology Cells Cellular immunotherapy Clinical Collaborations Complex Computer Analysis Data Data Analyses Development Effectiveness Engineering Environment Extracellular Matrix Fingerprint Genetically Engineered Mouse Genome engineering Goals Image Imaging technology Immune response Immunosuppression Immunotherapy Infrastructure Institution Leadership Malignant Neoplasms Malignant neoplasm of brain Malignant neoplasm of pancreas Microscopy Modeling Molecular Oncology Optics Persons Play Prognosis Publishing Regimen Research Resolution Seminal Solid Neoplasm Spectrum Analysis Sum T cell therapy T-Lymphocyte Technology Testing Time Tissue imaging Tissues Tumor Immunity Tumor-infiltrating immune cells Vision Work anti-tumor immune response biophysical model cancer imaging cancer immunotherapy cancer therapy cell behavior cellular engineering cellular imaging crosslink data modeling design engineered T cells experience fluorescence lifetime imaging imaging platform immune checkpoint blockade immune function improved instrumentation meetings member migration molecular imaging multimodality multiparametric imaging multiphoton microscopy nanofabrication neoplasm immunotherapy new technology next generation novel optical imaging response technology development tool tumor tumor immunology tumor microenvironment tumor-immune system interactions virtual

项目摘要

This project proposes an integrated suite of microscopy and data analysis advances that would enable quantitative, mechanistic analysis of immune-microenvironment dynamics in poor prognosis solid tumors. While immunotherapies are showing remarkable clinical responses in some advanced cancers, to date, their impact on many solid tumors has been modest. This is due, in part, to solid tumor microenvironments limiting the effectiveness of natural immune responses and immunotherapies. Yet, our understanding of the physical and molecular mechanisms governing T cell infiltration, distribution, and function in native tumor microenvironments remains extremely limited. As such, defining key T cell behaviors as a function of complex tumor microenvironments will identify design criteria that can be used to develop novel cell engineering strategies that optimize T cell-centric therapies for solid tumors. To this end the research theme of the U54 Center for Multiparametric Imaging of Tumor Immune Microenvironments (C-MITIE) is to define physical and molecular barriers to effective anti-tumor immunity and immunotherapies through advancement and development of state-of-the-art live cell and tissue optical imaging platforms and quantitative analyses. To achieve our goals, our framework brings together advanced optical imaging platforms, nano- and micro- fabrication, genome engineering, cancer immunology, and biophysical modeling. Thus, from this integrated effort we seek to define mechanisms of immune suppression that guide the development of next-generation cell-based immunotherapies.

该项目提出了一套集成的显微镜和数据分析进步，将使预后不良实体瘤免疫微环境动态的定量、机制分析。虽然免疫疗法在一些晚期癌症中显示出显着的临床反应，但迄今为止，它们的疗效对许多实体瘤的影响不大。这部分是由于实体瘤微环境限制自然免疫反应和免疫疗法的有效性。然而，我们对物理的理解以及控制天然肿瘤中 T 细胞浸润、分布和功能的分子机制微环境仍然极其有限。因此，将关键 T 细胞行为定义为复杂的函数肿瘤微环境将确定可用于开发新型细胞工程的设计标准优化以 T 细胞为中心的实体瘤疗法的策略。为此U54的研究主题肿瘤免疫微环境多参数成像中心 (C-MITIE) 旨在定义物理和免疫微环境通过先进和有效的抗肿瘤免疫和免疫治疗的分子障碍开发最先进的活细胞和组织光学成像平台和定量分析。到为了实现我们的目标，我们的框架汇集了先进的光学成像平台、纳米和微米制造、基因组工程、癌症免疫学和生物物理建模。因此，从这个综合我们努力定义指导下一代发育的免疫抑制机制基于细胞的免疫疗法。