Harnessing the Tumor Immune Microenvironment of Brain Metastases
Nearly 40% of patients with melanoma will develop brain metastases (MBM). MBM can reduce overall survival and predict poor outcomes, even after immunotherapy treatment. Radiation therapy (RT) against MBM injures neurons and initiates inflammation in the brain. CD8+ T cells are recruited to sites of injury and may infiltrate MBM. The inflammatory environment can change how MBMs form after RT. If CD8+ T cells responses and inflammatory changes are better understood, this could inform treatments for MBM after RT. We will use a mouse model of MBM to compare how many and what type of CD8+ T cells attack tumors growing in irradiated compared to unirradiated brains. We will also test effects of drugs, called dual checkpoint inhibitors and beta adrenergic receptor inhibitors, on the amount of type of detected CD8+ T cells. These studies may reveal novel therapeutic approaches for patients whose disease progresses in the brain after RT.
