Review
. 2019 Dec; 58(Suppl 7):vii59-vii67.
doi: 10.1093/rheumatology/kez308.

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

Sophia C Weinmann 1 David S Pisetsky 1 
Affiliations
  • PMID: 31816080
  •     70 References
  •     43 citations

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.

Keywords: B cell; CTLA-4; PD-1; PD-L1; T cell; arthritis; autoantibodies; autoreactivity; checkpoint; co-stimulation.

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Cancers (Basel), 2022 Feb 16; 14(3). PMID: 35159059    Free PMC article.
Review.
Immune checkpoint inhibitor induced thyroid dysfunction is a frequent event post-treatment in NSCLC.
Nanruoyi Zhou, Maria A Velez, +14 authors, Aaron Lisberg.
Lung Cancer, 2021 Sep 11; 161. PMID: 34507111    Free PMC article.
Cardiotoxicity risk factors with immune checkpoint inhibitors.
Zachary L Brumberger, Mary E Branch, +3 authors, Sujethra Vasu.
Cardiooncology, 2022 Mar 13; 8(1). PMID: 35277208    Free PMC article.
Checkpoint Inhibitors and Induction of Celiac Disease-like Condition.
Aaron Lerner, Carina Benzvi.
Biomedicines, 2022 Mar 26; 10(3). PMID: 35327411    Free PMC article.
Review.
Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis.
Alejandro Olivares-Hernández, Edel Del Barco Morillo, +8 authors, María Dolores Ludeña de la Cruz.
Biomedicines, 2022 Feb 26; 10(2). PMID: 35203569    Free PMC article.
Depletion of tumor associated macrophages enhances local and systemic platelet-mediated anti-PD-1 delivery for post-surgery tumor recurrence treatment.
Zhaoting Li, Yingyue Ding, +7 authors, Quanyin Hu.
Nat Commun, 2022 Apr 08; 13(1). PMID: 35387972    Free PMC article.
Association of Blood Biochemical Indexes and Antibiotic Exposure With Severe Immune-related Adverse Events in Patients With Advanced Cancers Receiving PD-1 Inhibitors.
Lijun Zhao, Yang Li, +11 authors, Xia He.
J Immunother, 2022 Mar 08; 45(4). PMID: 35250004    Free PMC article.
Exploring the Mechanisms Underlying the Cardiotoxic Effects of Immune Checkpoint Inhibitor Therapies.
Daniel Ronen, Aseel Bsoul, +4 authors, Rabea Asleh.
Vaccines (Basel), 2022 Apr 24; 10(4). PMID: 35455289    Free PMC article.
Review.
Nivolumab Combined With Ipilimumab Treatment Induced Hypophysitis and Immune-Mediated Liver Injury in Advanced Esophageal Squamous Cell Carcinoma: A Case Report.
Yi Feng, Chengyang Li, +4 authors, Tianshu Liu.
Front Oncol, 2022 Apr 19; 12. PMID: 35433482    Free PMC article.