C1: Vascular control of tumor immunity in the CNS

Michael Platten / Katharina Sahm

One major challenge in brain tumor immunotherapy is to ensure homing of peripherally activated adaptive immune cells to the tumor while retaining their effector function. Here, the brain tumor vasculature plays an important role in regulating T cell transmigration and activity. While the plasticity of the brain tumor vaculature and its effects on the tumor microenvironment are well understood tumor vasculature-mediated mechanisms that control T cell transmigration and function are less clear. Therapeutic measures targeting these mechanisms represent an attractive strategy to enhance immunotherapy of brain tumors. Preliminary work for this project shows synergistic effects of T cell- based immunotherapy and low-dose tumor irradiation in a syngeneic murine glioma model and suggests the vascular compartment as key mediator of radiation-induced immune stimulation. In addition, expression profiling of human glioblastoma tissue confirmed an inflammatory gene signature in blood vessels of recurrent brain tumors after local radiotherapy and identified potential endothelial factors dictating immune cell transmigration and effector function in the CNS. These factors will be validated with the help of animal models of experimental autoimmune encephalomyelitis and genetically modified murine glioma models. Clinically relevant treatment approaches such as low dose tumor irradiation and T cell immunotherapy will be used to study the endothelial – immune cell interface. This will allow identifying novel angiocrine factors driving T cell transmigration and function within the CNS.