Prospects of immune checkpoint modulators in the treatment of glioblastoma

Matthias Preusser, Michael Lim, David A. Hafler, David A. Reardon, John H. Sampson

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)504-514
Number of pages11
JournalNature Reviews Neurology
Volume11
Issue number9
DOIs
StatePublished - Sep 7 2015

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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