Speaker
Description
The ovarian tumor microenvironment is shaped by dynamic interactions among cancer, stromal, and immune cells, but the drivers of progression remain unclear. In ovarian cancer, we found that immune balance is more prognostic than absolute immune cell abundance: CD8/Treg and CD8/CD4 ratios were more strongly associated with survival than CD8+, CD4+, or Treg levels alone. Macrophage state was also critical. Tumors enriched in M2 macrophages were linked to vascular invasion, persistent disease, and worse survival, whereas higher M0 macrophage levels predicted better outcomes; M1 macrophages showed little prognostic value. Neutrophil infiltration, though less common, was likewise associated with poor survival. Unsupervised clustering identified four immune-defined subtypes, with the worst outcomes in tumors enriched for M2 macrophages and CD4+ T cells and depleted in M0 macrophages. To investigate the dynamics of some of these players mechanistically, we pair patient-derived observations with a three-dimensional tumoroid model of ovarian cancer invasion and a baseline ODE model describing the coupled dynamics of ovarian cancer cells, stromal cells, macrophages, and mesothelial invasion. This experimental–mathematical framework allows us to examine how these components interact and how those interactions may be leveraged to reduce tumor invasion.
