title: Emerging immunotherapies for glioblastoma.
abstract: BACKGROUND
  Immunotherapy for brain cancer has evolved dramatically over the past decade, owed in part to our improved understanding of how the immune system interacts with tumors residing within the central nervous system (CNS). Glioblastoma (GBM), the most common primary malignant brain tumor in adults, carries a poor prognosis (<15 months) and only few advances have been made since the FDA's approval of temozolomide (TMZ) in 2005. Importantly, several immunotherapies have now entered patient trials based on promising preclinical data, and recent studies have shed light on how GBM employs a slew of immunosuppressive mechanisms that may be targeted for therapeutic gain. Altogether, accumulating evidence suggests immunotherapy may soon earn its keep as a mainstay of clinical management for GBM.
  
  
  METHODS
  Here, we review cancer vaccines, checkpoint inhibitors, adoptive T-cell immunotherapy, and oncolytic virotherapy.
  
  
  CONCLUSIONS
  Checkpoint blockade induces antitumor activity by preventing negative regulation of T-cell activation. This platform, however, depends on an existing frequency of tumor-reactive T cells. GBM tumors are exceptionally equipped to prevent this, occupying low levels of antigen expression and elaborate mechanisms of immunosuppression. Therefore, checkpoint blockade may be most effective when used in combination with a DC vaccine or adoptively transferred tumor-specific T cells generated ex vivo. Both approaches have been shown to induce endogenous immune responses against tumor antigens, providing a rationale for use with checkpoint blockade where both primary and secondary responses may be potentiated.
authors.affiliation: a Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery , Duke University Medical Center , Durham , NC , USA.|b The Preston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , NC , USA.
authors.forename: Rupen
authors.initials: R
authors.lastname: Desai
authors.affiliation: a Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery , Duke University Medical Center , Durham , NC , USA.|b The Preston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , NC , USA.|c Department of Pathology , Duke University Medical Center , Durham , NC , USA.
authors.forename: Carter M
authors.initials: CM
authors.lastname: Suryadevara
authors.affiliation: a Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery , Duke University Medical Center , Durham , NC , USA.|b The Preston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , NC , USA.|c Department of Pathology , Duke University Medical Center , Durham , NC , USA.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Batich
authors.affiliation: a Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery , Duke University Medical Center , Durham , NC , USA.|b The Preston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , NC , USA.
authors.forename: S Harrison
authors.initials: SH
authors.lastname: Farber
authors.affiliation: a Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery , Duke University Medical Center , Durham , NC , USA.|b The Preston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , NC , USA.|c Department of Pathology , Duke University Medical Center , Durham , NC , USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez-Perez
authors.affiliation: a Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery , Duke University Medical Center , Durham , NC , USA.|b The Preston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , NC , USA.|c Department of Pathology , Duke University Medical Center , Durham , NC , USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
mesh_terms: D000328:Adult; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D050130:Oncolytic Virotherapy / Q000379:methods; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines
keywords: CDX-110; EGFRvIII; GBM; checkpoint inhibitor; chimeric antigen receptor t cells; dendritic cell vaccine; glioblastoma; glioblastoma multiforme; immune system; immunotherapy; ipilimumab; monoclonal antibody; nivolumab; oncolytic virus; peptide vaccine; rindopepimut; tumor lysate vaccine