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

Weinmann, Sophia C

Pisetsky, David S

2020-02-10T03:59:27Z

2020-02-10T03:59:27Z

2019-12

2020-02-10T03:59:26Z

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.

5670492

1462-0324

1462-0332

https://hdl.handle.net/10161/20067

eng

Oxford University Press (OUP)

Rheumatology (Oxford, England)

10.1093/rheumatology/kez308

B cell

CTLA-4

PD-1

PD-L1

T cell

arthritis

autoantibodies

autoreactivity

checkpoint

co-stimulation

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

Journal article

vii59

vii67

Supplement_7

School of Medicine

Duke

Medicine, Rheumatology and Immunology

Medicine

Clinical Science Departments

Duke Cancer Institute

Institutes and Centers

Duke Human Vaccine Institute

Immunology

Basic Science Departments

Published

58