Inflammatory Memory in the Brain Tumor Microenvironment after Radiotherapy
Immunotherapy holds great promise for cancer treatment but has had little impact on the management of primary and metastatic brain tumors. This is partly due to the unique immunology of the central nervous system (CNS). The CNS is considered immune privileged, meaning it has a weak cellular immune response. This is also the case with the brain tumor microenvironment. However, the brain tumor microenvironment does become inflamed after radiotherapy. This response can be very strong and is called radionecrosis. We hypothesize that the normal checkpoints that limit CNS inflammation are disrupted in radionecrosis. We will analyze surgically resected radionecrosis samples to uncover the inflammatory drivers of radionecrosis. We will also perform in vitro mechanistic studies using human neural tissue derived from pluripotent stem cells. This work aims to not only elucidate the molecular origins of radionecrosis but also to inform immune-based strategies for treating CNS malignancies.
