Mechano-Immunology in the Brain Tumor Microenvironment

Immunotherapy has provided curative outcomes in some cancers such as melanoma but has largely failed in patients suffering from glioblastoma, the most common and deadly primary brain tumor in adults. Poor therapeutic response may be mediated in part by the abnormal tumor microenvironment. In addition to well-studied chemical and biological atypia (e.g., leaky vasculature, hypoxia), the tumor microenvironment also harbors aberrant mechanical features. Like other solid tumors, glioblastoma exerts forces both within and outside the tumor. These abnormal mechanical forces compress tumor blood vessels, promote invasion, and even compromise neurological function and perfusion in the surrounding brain. The glioblastoma microenvironment is known to be immunosuppressive, e.g., by excluding tumor-fighting immune cells and/or rendering them dysfunctional. However, the role of mechanics on immune cells – and vice versa – is largely unknown.

The TIME Lab (Tumor Immune Microenvironment & Mechanics) seeks to answer these questions by studying “mechano-immunology” – a burgeoning field of cancer research at the interface of tumor biology, mechanobiology, and cancer immunology. We utilize state-of-the-art research techniques including clinically relevant animal and organotypic models, intravital imaging, multi-omics (e.g., single-cell sequencing), and multi-scale tools to causally determine the effects of mechano-immunology. Lead by Prof. Meenal Datta, our research efforts are aimed at understanding and targeting novel biophysical interactions in the glioblastoma microenvironment to improve immunotherapeutic outcomes.