Grant: Project Grant

Glioblastoma is a highly aggressive and fatal type of brain cancer that has limited therapeutic options. While many other types of cancer have benefitted from the development of immune checkpoint inhibitors, clinical trials in glioblastoma have failed. This is because the immune cells that these therapies are meant to target are virtually absent in these tumors. Instead, another type of immune cell - the macrophage - is highly abundant in glioblastoma. Despite the general association of macrophage accumulation with unfavorable outcomes, our recent discovery highlights a specific subset of macrophages that exhibit potent anti-tumor properties. This beneficial subset can engulf and kill tumor cells, resulting in prolonged control of the tumor and a significant improvement in overall survival when present in high numbers. Therefore this proposal aims to unravel the mechanisms behind the remarkable tumouricidal activity of these specialized macrophages, with the goal of re-educating all macrophages in brain tumours to behave in a similar way. We will study specific behaviours that are toxic towards cancer, including tumour cell engulfment, and will uncover how these behaviours are regulated within the brain. Importantly, we will determine how to boost the production of these macrophages, thus providing insight into new and effective immune-targeted therapies in glioblastoma. In achieving these goals, we will address a critical need in the field of brain cancer therapeutics, where treatment options are extremely limited and patient mortality remains exceptionally high.