Abstract
Glioblastoma (GBM) is the most common and fatal primary central nervous system malignancy in adults with a median survival of less than 15 months. Surgery, radiation, and chemotherapy are the standard of care and provide modest benefits in survival, but tumor recurrence is inevitable. The poor prognosis of GBM has made the development of novel therapies targeting GBM of paramount importance. Immunotherapy via dendritic cells (DCs) has garnered attention and research as a potential strategy to boost anti-tumor immunity in recent years. As the “professional” antigen processing and presenting cells, DCs play a key role in the initiation of anti-tumor immune responses. Pre-clinical studies in GBM have shown long-term tumor survival and immunological memory in murine models with stimulation of DC activity with various antigens and costimulatory molecules. Phase I and II clinical trials of DC vaccines in GBM have demonstrated some efficacy in improving the median overall survival with minimal to no toxicity with promising initial results from the first Phase III trial. However, there remains no standardization of vaccines in terms of which antigens are used to pulse DCs ex vivo, sites of DC injection, and optimal adjuvant therapies. Future work with DC vaccines aims to elucidate the efficacy of DC-based therapy alone or in combination with other immunotherapy adjuvants in additional Phase III trials.
Highlights
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with an incidence rate of 3.2 per 100,000 [1]
Various molecules found in the tumor microenvironment (TME) and expressed by tumor cells inhibit dendritic cells (DCs) activation and drive DCs toward a suppressive, or regulatory phenotype including vascular endothelial growth factor (VEGF), PGE2, IL-10, and macrophage colony stimulating factor 1 (CSF-1) [97]
Given the crucial and unique role DCs play as the link between the innate and adaptive immune system, DC-based immunotherapy has been studied as a therapeutic approach in other systemic cancers with promising results [107,108,109,110]
Summary
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with an incidence rate of 3.2 per 100,000 [1]. With the other cases presenting originally as lower grade gliomas (secondary GBM) [2]. GBM portends a poor median survival of less than 2 years, despite the current standard of care of maximal surgical resection, adjuvant radiation, and chemotherapy [3,4,5]. Due to the lack of significant changes in survival outcomes with conventional therapies, immunotherapy, which modulates the host immune system to enhance anti-tumor response, has emerged as a major focus in the fields of oncology and neuro-oncology as a promising treatment strategy. By harnessing the immune system, immunotherapies strive to overcome the unique global immunosuppressive challenges induced by GBMs
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