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进步，将使 预后不良实体瘤免疫微环境动力学的定量、力学分析。 虽然免疫疗法在一些晚期癌症中显示出显著的临床反应，但到目前为止，他们的 对许多实体肿瘤的影响并不大。这在一定程度上是由于实体肿瘤微环境的限制。 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T细胞在自然肿瘤中的渗透、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细胞行为定义为复合体的函数 肿瘤微环境将确定可用于开发新的细胞工程的设计标准 优化实体瘤以T细胞为中心的治疗的策略。为此，U54的研究主题 肿瘤免疫微环境多参数成像中心(C-MITIE)是为了定义物理和 分子屏障对有效的抗肿瘤免疫和免疫治疗的促进作用 最先进的活细胞和组织光学成像平台的开发和定量分析。至 为了实现我们的目标，我们的框架将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 我们努力定义免疫抑制机制，以指导下一代的发展 基于细胞的免疫疗法。

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.