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

• Published in: Rheumatology (Oxford, England) Vol. 58; no. Supplement_7; pp. vii59 - vii67
• Main Authors: Weinmann, Sophia C, Pisetsky, David S
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2019
• Subjects: Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - pharmacology; Antineoplastic Agents, Immunological - therapeutic use; Autoimmune Diseases - chemically induced; Autoimmune Diseases - immunology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - immunology; Humans; Immunologic Factors - adverse effects; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Immunotherapy - adverse effects; Immunotherapy - methods; Lymphocyte Activation - drug effects; Neoplasms - drug therapy; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Rheumatic Diseases - chemically induced; Rheumatic Diseases - immunology; Supplement; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tumor Escape - drug effects; Tumor Escape - immunology; checkpoint; B cell; autoreactivity; arthritis; T cell; PD-L1; CTLA-4; co-stimulation; PD-1; autoantibodies
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/kez308

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.