Role of Regulatory T cells in shaping the tumor microenvironment spatial organization

Regulatory T cells (Tregs) are a critical component of solid tumors, contributing to an immunosuppressive tumor microenvironment (TME). A comprehensive understanding of the mechanisms by which Tregs shape the TME and the factors influencing responses to Treg-targeted therapies remains elusive. Our research focuses on deciphering the complex interactions within the TME and understanding how Tregs influence its spatial organization. In this POC study, we aim to establish methodologies to uncover the intricate web of immune interactions within the TME. Leveraging the PhenoCycler-Fusion System (CODEX), we will perform a spatial characterization of the immune TME of two distinct tumor models, with varying sensitivities to Treg-mediated suppression. Subsequently, we will investigate the impact of Tregs on the spatial organization of the TME. By employing inducible genetic mouse models and Treg-depleting monoclonal antibodies, we will elucidate how Treg elimination influences the immune composition, pathways, and interactions within the TME. This research has the potential to significantly enhance our knowledge of immune surveillance mechanisms and the spatial dynamics of the TME. It may offer new insights into the mechanisms of Treg-mediated tumor immune suppression, potentially optimizing Tregtargeted therapies. Furthermore, we anticipate identifying specific immune cell interactions that could serve as valuable therapeutic targets, paving the way for the development of novel immune cell-based therapies to enhance anti-tumor immunity.