Endocrinol Metab.  2022 Dec;37(6):839-850. 10.3803/EnM.2022.1627.

Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society

• Kwon H
• Roh E
• Ahn CH
• Kim HK
• Ku CR
• Jung KY
• Lee JH
• Kim EH
• Suh S
• Hong S
• Ha J
• Moon JS
• Kim JH
• Kim Mk
• The Committee of Clinical Practice Guideline of the Korean Endocrine Society

• KMID: 2537284
• DOI: http://doi.org/10.3803/EnM.2022.1627

Abstract

Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Keyword

Adrenal glands; Pituitary gland; Thyroid gland; Immune checkpoint inhibitors; Drug-related side effects and adverse reactions; Endocrine system diseases

Figure

• 

  Fig. 1. The mechanisms of action of immune checkpoint inhibitors (ICIs). The binding of major histocompatibility complex (MHC)-peptide and T-cell receptor (TCR) activates the anti-cancer pathway of T-cell mediated immune response. Cancer cells suppress the activity of T-cells that are specific for tumor antigens as one of the immune escape mechanisms by changing the immune checkpoint function. The binding of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to its ligand and programmed cell death protein 1 (PD-1) to programmed death-ligand 1 (PD-L1) inhibit the anti-cancer activity (tumor escape). The binding of monoclonal antibodies (Abs) to CTLA-4, PD-1, or PD-L1 prevent the inhibition of the anti-cancer pathway, and promote T-cell activation and elimination of tumor cells.

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