Immunomodulation by Laser Interstitial Thermal Therapy (LITT) in mouse brain
Laser Interstitial Thermal Therapy (LITT) is a minimally invasive neurosurgical procedure that uses an MRI-guided laser fiber for selective heat destruction of brain tumors. LITT is the only option for patients with inoperable brain tumors. LITT causes prolonged opening of the blood-brain barrier (BBB) and blood-tumor barrier (BTB) which allows immune cells to passage from the blood into the brain and brain tumor tissues. This ability of LITT to induce a temporary leakiness of the BBB/BTB may offer new applications of LITT in immunotherapy. We hypothesize that LITT serves as a new immunomodulator by generating immunogenic debris from the heat-induced destruction of brain tumor cells that attracts and stimulates immune cells to create a tumor hostile brain tumor microenvironment. We will establish the first LITT brain tumor mouse model in Canada and study the immunomodulatory role of LITT in different brain tumor mouse models. The LITT effects on specific immune cell populations and the BBB and BTB cellular composition in brain tumors is studied at defined time points. This includes gene expression profiling of LITT-induced changes in cell composition directly in the brain tumor microenvironment.