Cancer Immunotherapy Related Endocrine Adverse Effects

Hana Kim; Sun Wook Cho; Young Joo Park

doi:10.11106/ijt.2019.12.2.97

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Kim, Cho, and Park: Cancer Immunotherapy Related Endocrine Adverse Effects

Review Article

International Journal of Thyroidology 2019; 12(2): 97-104.

Published online: 30 November 2019

DOI: https://doi.org/10.11106/ijt.2019.12.2.97

Cancer Immunotherapy Related Endocrine Adverse Effects

Hana Kim¹, Sun Wook Cho^1,², Young Joo Park^1,²

¹Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

²Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Correspondence: Young Joo Park, MD, PhD, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Tel: 82-2-2072-4183, Fax: 82-2-764-2199, yjparkmd@snu.ac.kr

Received 30 July 2019 Revised 10 October 2019 Accepted 10 October 2019

The Korean Thyroid Association

(open-access):

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cancer immunotherapy has emerged as a promising therapy for a wide variety of tumors. Immune checkpoint inhibitors including anti cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and programmed death ligand-1 (PD-L1) monoclonal antibodies have proven to be especially effective in various advanced cancers. However, cancer the immunotherapy disturbs the immune system and may also cause immune related side effects (IRAE) distinguished from cytotoxic chemotherapy toxicity. Among them, endocrine IRAE has been reported with a higher incidence than other organ IRAE. We focus on the most relevant and new aspects related to endocrine IRAE due to cancer immunotherapy in this review.

Keywords: Programmed cell death receptor 1 (PD-1), Programmed cell death receptor ligand 1 (PD-L1), Cytotoxic T-lymphocyte-associated antigen 4, Immune related adverse effect (IRAE)

Figures and Tables

Fig. 1

Mechanism of immune checkpoint inhibitors (Adopted and modified from reference 37). Immune checkpoints are receptors for T lymphocytes which modulate the immune system after binding ligands, either stimulating or inhibiting T cell response. Co-stimulatory immune control points, such as Cluster of Differentiation 28 (CD28), Inducible T-cell COStimulator (ICOS), and Cluster of Differentiation 46 (CD46), are induced by the activated antigen presenting cells (APCs). In contrary, there are two main co-inhibitory immune control points, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death receptor 1 (PD-1). CTLA-4 is expressed on the surface of most activated T lymphocytes during the initial activation phase in lymphatic tissue by dendritic cells and by other APCs. It inhibits periepheral T cell activation, leading to immune tolerance through negative signaling and competitive antagonism of the CD28/B7-mediated co-stimulatory pathway. PD-1 is another co-inhibitory receptor expressed in activated T cell during the effector phase. The binding of PD-1 to its PD-L1 (B7-H1) and PD-L2 (B7-DC) ligands tissue macrophages inhibits T lymphocyte activation facilitating immunological tolerance. Therefore, anti PD-1/PD-L1 and anti CTLA-4 inhibitors facilitate T cell activation and show antitumor effects.

Table 1

Toxicity grading of endocrine IRAEs of ICIs according to Common Terminology Criteria for Adverse Events (CTCAE) of National Institutes of Health (NIH) (Adopted and modified from reference 38)

^aGrade of IRAEs has been estimated according to Common Terminology Criteria for Adverse Events (CTCAE) grading scale; grade 5 relates to death for each IRAE.

ADL: activities of daily living, CCS: corticosteroid, FT4: free thyroxine, ICIs: immune checkpoint inhibitors, MRI: magnetic resonance imaging, NSAIDs: nonsteroidal anti-inflammatory drugs, T1DM: type1 diabetes mellitus, TSH: thyroid stimulating hormone

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