Burchett : Elucidating Abnormal Myeloid-Mechanical Interactions in Glioblastoma
Elucidating Abnormal Myeloid-Mechanical Interactions in Glioblastoma
University of Notre Dame
Alice Burchett, University of Notre Dame
Prof. Meenal Datta, University of Notre Dame
The glioblastoma microenvironment is highly immunosuppressive and features growth-induced compressive solid stress. Macrophages can make up nearly half of the tumor bulk and contribute to immunosuppression, making them an attractive therapeutic target. This work aims to understand how solid stress affects macrophage phenotype, and how macrophages in turn contribute to solid stress.
To assess the macrophage response to compression, a weight is applied to the cells to apply 0.15 kPa of solid stress, within the range found in brain tumors. To determine their contribution to solid stress, macrophages are embedded in a 1% agarose gel, where they proliferate to form spheroids, displacing the surrounding gel. The magnitude of stress generated from this displacement can be quantified either by imaging the displacement of embedded fluorescent microbeads, or by importing a 3D model of the spheroid to COMSOL to obtain a simulated stress field.
Preliminary results suggest that compression of macrophages alters the expression of canonical polarization markers. Macrophages embedded in agarose proliferate and generate solid stress. Further investigation is required to determine the functional macrophage response to solid stress, and to quantify macrophages’ ability to generate stress in different conditions.
This work suggests that macrophages can sense and respond to the magnitude of solid stress that is found in brain tumors, and also that macrophages may themselves be responsible for some of this stress. Further understanding of the reciprocal regulation of macrophages and solid stress may highlight new therapeutic approaches for glioblastoma.
Translational/Human Health Impact:
Understanding and overcoming immunosuppression could tip the balance towards a successful anti-tumor immune response and improved patient outcomes for glioblastoma as well as other solid tumors. These in vitro models of solid stress can also be tuned for other tumor and disease types and used to screen drugs for their impact on the mechanical tumor microenvironment.