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Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors

Authors
  • Weinmann, Sophia C1
  • Pisetsky, David S1, 2
  • 1 Division of Rheumatology and Immunology, Duke University Medical Center, USA , (United States)
  • 2 Medical Research Service, VA Medical Center, USA , (United States)
Type
Published Article
Journal
Rheumatology (Oxford, England)
Publisher
Oxford University Press
Publication Date
Dec 09, 2019
Volume
58
Issue
Suppl 7
Identifiers
DOI: 10.1093/rheumatology/kez308
PMID: 31816080
PMCID: PMC6900913
Source
PubMed Central
Keywords
License
Unknown

Abstract

Immune checkpoint inhibitors are novel biologic agents to treat cancer by inhibiting the regulatory interactions that limit T cell cytotoxicity to tumours. Current agents target either CTLA-4 or the PD-1/PD-L1 axis. Because checkpoints may also regulate autoreactivity, immune checkpoint inhibitor therapy is complicated by side effects known as immune-related adverse events (irAEs). The aim of this article is to review the mechanisms of these events. irAEs can involve different tissues and include arthritis and other rheumatic manifestations. The frequency of irAEs is related to the checkpoint inhibited, with the combination of agents more toxic. Because of their severity, irAEs can limit therapy and require immunosuppressive treatment. The mechanisms leading to irAEs are likely similar to those promoting anti-tumour responses and involve expansion of the T cell repertoire; furthermore, immune checkpoint inhibitors can affect B cell responses and induce autoantibody production. Better understanding of the mechanisms of irAEs will be important to improve patient outcome as well as quality of life during treatment.

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