The potential for immune checkpoint modulators in cerebrovascular injury and inflammation

Expert Opin Ther Targets. 2021 Feb;25(2):101-113. doi: 10.1080/14728222.2021.1869213. Epub 2021 Jan 4.

Abstract

Introduction: Neuroinflammation has been linked to poor neurologic and functional outcomes in many cerebrovascular disorders. Immune checkpoints are upregulated in the setting of traumatic brain injury, intracerebral hemorrhage, ischemic stroke, central nervous systems vasculitis, and post-hemorrhagic vasospasm, and are potential mediators of pathologic inflammation. Burgeoning evidence suggests that immune checkpoint modulation is a promising treatment strategy to decrease immune cell recruitment, cytokine secretion, brain edema, and neurodegeneration.Areas covered: This review discusses the role of immune checkpoints in neuroinflammation, and the potential for therapeutic immune checkpoint modulation in inflammatory cerebrovascular disorders. A search of Pubmed and clinicaltrials.gov was performed to find relevant literature published within the last 50 years.Expert opinion: The clinical success of immune-activating checkpoint modulators in human cancers has shown the immense clinical potential of checkpoint-based immunotherapy. Given that checkpoint blockade can also precipitate a pathologic pro-inflammatory or autoimmune response, it is plausible that these pathways may also be targeted to quell aberrant inflammation. A limited but growing number of studies suggest that immune checkpoints play a critical role in regulating the immune response in the central nervous system in a variety of contexts, and that immune-deactivating checkpoint modulators may be a promising treatment strategy for acute and chronic neuroinflammation in cerebrovascular disorders.

Keywords: Checkpoint agonist; immune checkpoint; immunotherapy; intracerebral hemorrhage; neuroinflammation; traumatic brain injury; vasculitis; vasospasm.

Publication types

  • Review

MeSH terms

  • Animals
  • Cerebrovascular Disorders / drug therapy*
  • Cerebrovascular Disorders / immunology
  • Cerebrovascular Disorders / physiopathology
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Proteins / immunology
  • Immunologic Factors / pharmacology
  • Immunotherapy / methods*
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / pathology
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / immunology

Substances

  • Immune Checkpoint Inhibitors
  • Immune Checkpoint Proteins
  • Immunologic Factors