Manipulating the tumor immune microenvironment towards an anti-tumor response

• Summary: We use biomaterials to mimic or modulate the tumor microenvironment. Two current areas of study include mimicking the dynamic stiffening of the extracellular matrix (ECM) as tumors progress and modulating the tumor immune microenvironment using immunostimulatory nanoparticles.
• As tumor progress, they become stiffer – this is why some breast tumors can be found via palpation. Previous 3D models were unable to appropriately model the changes in ECM stiffness observed in cancer. We have developed a 3D hydrogel cell culture system that can be stiffened with exposure to light. This system allows us to begin cell culture in a soft, healthy mammary tissue ECM environment and progressively stiffen the ECM to mimic the stiffness seen at early tumorigenesis. Thus far, we have seen that breast tumor cells become more invasive and migratory in stiffer environments.
• Macrophages are one of the most populous immune cells in many solid tumors. They help establish and maintain the immunosuppressive tumor microenvironment that facilitates tumor growth and prevents a successful immune response. We are studying how macrophages acquire this unique, tumor associated-macrophage phenotype through components like ECM stiffness, tumor-derived exosomes, and lactic acid. Additionally, we are studying how we can use immunostimulatory nanoparticles to reprogram these macrophages into pro-inflammatory, anti-tumor macrophages to decrease tumor burden.