Simple SummaryAlthough the immune system can mount effective responses against antigens within the CNS, this does not occur in the context of high-grade gliomas. Considered to be the primary antigen presenters, dendritic cells (DC) are essential for initiating antitumor immune responses through tumor antigen and presentation to T cells and through the secretion of chemokines for T cell migration. Many immunotherapies depend on antigen presentation by dendritic cells, yet dendritic cells are understudied in the specific context of brain tumors such as high-grade gliomas. Accordingly, this review summarizes the presence and function of dendritic cells within the tumor microenvironment of high-grade gliomas with special consideration of therapeutic opportunities.AbstractHigh-grade gliomas are malignant brain tumors, and patient outcomes remain dismal despite the emergence of immunotherapies aimed at promoting tumor elimination by the immune system. A robust antitumor immune response requires the presentation of tumor antigens by dendritic cells (DC) to prime cytolytic T cells. However, there is a paucity of research on dendritic cell activity in the context of high-grade gliomas. As such, this review covers what is known about the role of DC in the CNS, DC infiltration of high-grade gliomas, tumor antigen drainage, the immunogenicity of DC activity, and DC subsets involved in the antitumor immune response. Finally, we consider the implications of suboptimal DC function in the context of immunotherapies and identify opportunities to optimize immunotherapies to treat high-grade gliomas.