Center for Multiparametric Imaging of Tumor Immune Microenvironments

该项目提出了一套集成的显微镜和数据分析的进步， 预后不良的实体瘤中免疫微环境动力学的定量、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， 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了 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T细胞浸润、分布和功能的分子机制 微环境仍然非常有限。因此，将关键T细胞行为定义为复杂的功能， 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治疗策略。为此，U 54的研究主题 肿瘤免疫微环境多参数成像中心（C-MITIE）将定义物理和 有效的抗肿瘤免疫和免疫治疗的分子屏障， 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 我们试图确定免疫抑制的机制，指导下一代的发展， 细胞免疫疗法

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.