Dynamic Spatiotemporal Analysis of Immune Cells in the Tumor Microenvironment

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。

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.