Abstract
INTRODUCTION: Despite maximal surgical resection and chemoradiation, glioblastoma (GBM) continues to be associated with significant morbidity and mortality. Novel therapeutic strategies are urgently needed. Given success in treating multiple other forms of cancer, checkpoint inhibitor immunotherapy remains foremost amongst novel therapeutic strategies that are currently under investigation. AREAS COVERED: Through a systematic review of both published literature and the latest preliminary data available from ongoing clinical studies, we provide an up-to-date discussion on the immune system in the CNS, a detailed mechanistic evaluation of checkpoint biology in the CNS along with evidence for disruption of these pathways in GBM, and a summary of available preclinical and clinical data for checkpoint blockade in GBM. We also include a discussion of novel, emerging targets for checkpoint blockade which may play an important role in GBM immunotherapy. EXPERT OPINION: Evidence indicates that while clinical success of checkpoint blockade for the treatment of GBM has been limited to date, through improved preclinical models, optimization in the context of standard of care therapies, assay standardization and harmonization, and combinatorial approaches which may include novel targets for checkpoint blockade, checkpoint inhibitor immunotherapy may yield a safe and effective therapeutic option for the treatment of GBM.