Mechanisms of immune suppression in glioblastoma

Despite advances in immunotherapy for other solid tumors, glioblastoma multiforme (GBM), the most common malignant primary brain tumor, has thus far demonstrated resistance to novel immunotherapeutics such as immune checkpoint inhibitors. In GBM, resistance to immunotherapy may be partly attributable to the immunosuppression that is characteristic of this disease. Both tumor-driven and iatrogenic mechanisms of immune suppression affect systemic immune status as well as the tumor microenvironment in patients with GBM. A thorough understanding of the pathophysiology of immunosuppression in GBM is needed to develop strategies to overcome resistance to immunotherapy in this disease. This chapter summarizes GBM-induced changes in circulating immune cell populations and in the tumor microenvironment and discusses how commonly used interventions in GBM patients, including radiation, chemotherapy, and corticosteroids, also result in immunosuppression.