title: Prospects of immune checkpoint modulators in the treatment of glioblastoma.
abstract: Glioblastoma is the most common primary brain tumour in adults. Prognosis is poor: even with the current gold-standard first-line treatment—maximal safe resection and combination of radiotherapy with temozolomide chemotherapy—the median overall survival time is only approximately 15-17 months, because the tumour recurs in virtually all patients, and no commonly accepted standard treatment for recurrent disease exists. Several targeted agents have failed to improve patient outcomes in glioblastoma. Immunotherapy with immune checkpoint inhibitors such as ipilimumab, nivolumab, and pembrolizumab has provided relevant clinical improvements in other advanced tumours for which conventional therapies have had limited success, making immunotherapy an appealing strategy in glioblastoma. This Review summarizes current knowledge on immune checkpoint modulators and evaluates their potential role in glioblastoma on the basis of preclinical studies and emerging clinical data. Furthermore, we discuss challenges that need to be considered in the clinical development of drugs that target immune checkpoint pathways in glioblastoma, such as specific properties of the immune system in the CNS, issues with radiological response assessment, and potential interactions with established and emerging treatment strategies.
authors.affiliation: Department of Medicine I and Comprehensive Cancer Centre CNS Tumours Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.affiliation: Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lim
authors.affiliation: Department of Neurology, Yale School of Medicine, Yale New Haven Hospital, 15 York Street, PO Box 208018, New Haven, CT 06520, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.affiliation: Center for Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana 2134, Boston, MA 02215, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Division of Neurosurgery, 220 Sands Building, Research Drive, Duke University School of Medicine, Durham, NC 27705, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*
chemical_list: D007155:Immunologic Factors