Patients suffering from glioblastoma – the deadliest primary brain tumor in adults – have a dismal median overall survival rate of less than 2 years despite aggressive available treatments. The tumor microenvironment may be largely responsible for poor therapeutic outcomes as it harbors mechanopathologies that drive disease progression and treatment resistance. One such feature is “solid stress” – a mechanical force originating from cells and extracellular matrix – that can compress blood vessels, induce hypoxia and immunosuppression, and hinder drug delivery and efficacy. Confined and compounded within the rigid skull, solid stress from brain tumors like glioblastoma can also cause debilitating neurological dysfunction. Here, I will present findings from patients and mouse models of glioblastoma that show how solid stress: i) can be measured and/or applied in vivo, ii) can damage the healthy brain tissue surrounding the tumor, and iii) can be targeted to restore neurological function and overcome resistance to therapies such as immune checkpoint blockade.

Short Bio: 
Dr. Meenal Datta is a postdoctoral research fellow in the Edwin L. Steele Laboratories for Tumor Biology at Massachusetts General Hospital/Harvard Medical School. She received her Ph.D. in Chemical and Biological Engineering from Tufts University in 2018.  

Dr. Datta specializes in mechanism-based preclinical research that has the potential to be rapidly translated to improve treatment approaches in the clinic. Leveraging her multidisciplinary training and experience, Dr. Datta has characterized the abnormal tissue microenvironments that present in a variety of diseases ranging from virulent tuberculosis to benign schwannoma to deadly glioblastoma. These diseases, though seemingly disparate, share unifying microenvironmental features including abnormal blood vessels, abundant extracellular matrix, immunosuppression, and mechanopathologies. In her Ph.D. work, Dr. Datta discovered that pulmonary tuberculosis granulomas harbor an aberrant vasculature that can be targeted using antiangiogenic agents – originally approved for cancer treatment – to improve drug delivery. In her postdoctoral training, Dr. Datta is utilizing novel approaches to reprogram the immunosuppressive glioblastoma microenvironment to improve immunotherapy response. This fall, Dr. Datta will begin a tenure track position at the University of Notre Dame and continue her work at the intersection of cancer biology, mechanobiology, and immunology.