Dr. Candice Poon

Perivascular stromal cells modulate immune cell trafficking in glioma

It is crucial to understand the tumor microenvironment in order to develop effective anticancer treatments. The tumor microenvironment consists of cancer cells, immune cells, and stroma. In solid tumors outside of the central nervous system (CNS), cancer-associated fibroblasts (CAFs) comprise a large component of the stroma. CAFs have diverse tumor-promoting properties including contributing to treatment resistance, immunosuppression, and poorer patient prognosis. However, CAFs have only recently been discovered at the single-cell level in glioma. Our work has shown that many CAFs localize to the glioma perivascular space and play a central role in microvascular proliferation, a disease- and prognosis-defining histopathology in glioma. Based on this work, we believe the perivascular space is an important anatomical location because it serves as a busy interface between central and peripheral body systems. Not only is it a point of entry and exit for immune cells, but also of CAFs and other stromal cells originating outside of the CNS. Additionally, it is a location where cerebrospinal fluid (CSF) mixes with interstitial fluid that bathes the brain parenchyma, where important nutrients and metabolites are exchanged. However, the perivascular space is understudied. Thus, our laboratory is focused on studying the perivascular space using high dimensional techniques by characterizing the interactions between immune cells, CAFs, and other stromal cells in the context of a perivascular microenvironment bathed in CSF. Understanding the CNS perivascular microenvironment could not only lead to discoveries beyond the pathophysiology of microvascular proliferation, but elucidation of mechanisms that could help improve immune cell trafficking, immune surveillance, and the efficacy of currently available and novel anticancer therapies.