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.
This proposal aims to understand the mechanisms that tumors use to evade immunosurveillance by studying how immune cell remodeling over the course of tumor progression promotes an immunosuppressive tumor microenvironment. Findings from our study have the potential to identify new therapeutic targets for the development of novel and effective cancer treatment strategies.
