Tumor heterogeneity & Spatial organization of the anti-tumor immune response
Tumor heterogeneity is a barrier to an effective anti-tumor immune response. The Reeves Lab has established a powerful novel system to model tumor heterogeneity in vivo, in which we can establish and modulate heterogeneous tumors made up of multiple, fluorescently-labeled tumor populations. These fluorescent labels enable us to track each population within the tumor and study how heterogeneity influences the immune response in each region of a heterogeneous tumor. We have shown that tumor cells shape the intratumoral immune response on a highly localized spatial scale, in part through chemokines including CX3CL1. The spatial organization of tumor subpopulations thus creates an architectural blueprint for the locations and functions of tumor-infiltrating immune cells. We are actively studying the mechanisms tumor cells use to sculpt the local immune microenvironment, as well as how these distinct, spatially localized immune microenvironments within a heterogeneous tumor influence the response to immunotherapy.