PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Mustafa KhasrawJohn H Sampson

Abstract

Glioblastoma (WHO grade IV glioma) is the most common malignant primary brain tumor in adults. Survival has remained largely static for decades, despite significant efforts to develop new effective therapies. Immunotherapy and especially immune checkpoint inhibitors and programmed cell death (PD)-1/PD-L1 inhibitors have transformed the landscape of cancer treatment and improved patient survival in a number of different cancer types. With the exception of few select cases (e.g., patients with Lynch syndrome) the neuro-oncology community is still awaiting evidence that PD-1 blockade can lead to meaningful clinical benefit in glioblastoma. This lack of progress in the field is likely to be due to multiple reasons, including inherent challenges in brain tumor drug development, the blood-brain barrier, the unique immune environment in the brain, the impact of corticosteroids, as well as inter- and intratumoral heterogeneity. Here we critically review the clinical literature, address the unique aspects of glioma immunobiology and potential immunobiological barriers to progress, and contextualize new approaches to increase the efficacy of PD-1/PD-L1 inhibitors in glioblastoma that may identify gaps and testable relevant hypotheses for...Continue Reading

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Dec 1, 2020·Neuro-oncology·Mustafa KhasrawDavid M Ashley
Nov 13, 2020·Journal of Translational Medicine·Craig A LandQian Xie
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Feb 14, 2021·International Immunopharmacology·Abolfazl MaghrouniAmirhossein Sahebkar
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Feb 6, 2022·Current Oncology Reports·Carlen A YuenAya Haggiagi

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