Immune Checkpoints and Graves' Disease, Thyroid Eye Disease, and Orbital Myopathy: A Comprehensive Review

Overview

Journal J Ophthalmic Vis Res

Specialty Ophthalmology

Date 2024 Oct 3

PMID 39359534

Authors

Zahra Souri

Farzad Pakdel

Affiliations

Soon will be listed here.

Abstract

Immune checkpoints (ICPs) are essential regulators of the immune system, ensuring a delicate balance between self-tolerance and autoimmune responses. ICP therapy is a rapidly growing cancer treatment strategy that inhibits the interaction between ICPs and their ligands. This biological interaction increases the ability of the immune system in combating cancer. However, in some cases, the use of these agents may lead to immune hyperactivity and, subsequently, autoimmune diseases. Graves' disease (GD), thyroid eye disease (TED), and orbital myopathy are complex autoimmune disorders characterized by the production of autoantibodies. The emergence of these treatment-related adverse events underscore the critical need for a deeper understanding of the immune-checkpoint axis in autoimmune diseases. In this review article, we provide a comprehensive survey of the biological mechanisms of ICPs that are most frequently targeted in cancer therapy, including CTLA-4, PD-1, PDL-1, and LAG3. Furthermore, we investigate the latest scientific findings on the adverse events associated with the inhibition of these ICPs. This paper will particularly focus on the potential risks these complications pose to ocular and orbital tissues, which are a concern in the context of cancer treatment.

References

Pakdel F, Ghazavi R, Heidary R, Nezamabadi A, Parvizi M, Memar M . Effect of Selenium on Thyroid Disorders: Scientometric Analysis. Iran J Public Health. 2019; 48(3):410-420. PMC: 6570790. View

Freeman G, Long A, Iwai Y, Bourque K, Chernova T, Nishimura H . Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000; 192(7):1027-34. PMC: 2193311. DOI: 10.1084/jem.192.7.1027. View

Garon E, Rizvi N, Hui R, Leighl N, Balmanoukian A, Eder J . Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015; 372(21):2018-28. DOI: 10.1056/NEJMoa1501824. View

Ibis B, Aliazis K, Cao C, Yenyuwadee S, Boussiotis V . Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases. Front Immunol. 2023; 14:1197364. PMC: 10277501. DOI: 10.3389/fimmu.2023.1197364. View

Zhou N, Velez M, Bachrach B, Gukasyan J, Fares C, Cummings A . Immune checkpoint inhibitor induced thyroid dysfunction is a frequent event post-treatment in NSCLC. Lung Cancer. 2021; 161:34-41. PMC: 8923054. DOI: 10.1016/j.lungcan.2021.08.009. View

Bartalena L, Fatourechi V . Extrathyroidal manifestations of Graves' disease: a 2014 update. J Endocrinol Invest. 2014; 37(8):691-700. DOI: 10.1007/s40618-014-0097-2. View

Yamada H, Okajima F, Onda T, Fujimori S, Emoto N, Sugihara H . New-onset graves' disease after the initiation of nivolumab therapy for gastric cancer: a case report. BMC Endocr Disord. 2020; 20(1):132. PMC: 7449083. DOI: 10.1186/s12902-020-00613-5. View

Bawazeer A, Rahali W, Alsharif A, Alshehri M, Maksood L, Babkier A . Idiopathic Orbital Inflammation Treated With Rituximab Monotherapy. Cureus. 2023; 15(1):e33614. PMC: 9911136. DOI: 10.7759/cureus.33614. View

Mangaraj S, Choudhury A, Mohanty B, Baliarsinha A . Neurological manifestations of Graves' disease: A case report and review of the literature. J Neurosci Rural Pract. 2016; 7(1):153-6. PMC: 4750319. DOI: 10.4103/0976-3147.165393. View

10.

Tawbi H, Schadendorf D, Lipson E, Ascierto P, Matamala L, Castillo Gutierrez E . Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022; 386(1):24-34. PMC: 9844513. DOI: 10.1056/NEJMoa2109970. View

11.

Egen J, Allison J . Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity. 2002; 16(1):23-35. DOI: 10.1016/s1074-7613(01)00259-x. View

12.

Souri Z, Jochemsen A, Versluis M, Wierenga A, Nemati F, van der Velden P . HDAC Inhibition Increases HLA Class I Expression in Uveal Melanoma. Cancers (Basel). 2020; 12(12). PMC: 7763827. DOI: 10.3390/cancers12123690. View

13.

Huard B, Mastrangeli R, Prigent P, Bruniquel D, Donini S, Maigret B . Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc Natl Acad Sci U S A. 1997; 94(11):5744-9. PMC: 20850. DOI: 10.1073/pnas.94.11.5744. View

14.

Brunner M, Chambers C, Chan F, Hanke J, Winoto A, Allison J . CTLA-4-Mediated inhibition of early events of T cell proliferation. J Immunol. 1999; 162(10):5813-20. View

15.

Jeyakumar N, Etchegaray M, Henry J, Lelenwa L, Zhao B, Segura A . The Terrible Triad of Checkpoint Inhibition: A Case Report of Myasthenia Gravis, Myocarditis, and Myositis Induced by Cemiplimab in a Patient with Metastatic Cutaneous Squamous Cell Carcinoma. Case Reports Immunol. 2020; 2020:5126717. PMC: 7355354. DOI: 10.1155/2020/5126717. View

16.

Mohammadi P, Hesari M, Chalabi M, Salari F, Khademi F . An overview of immune checkpoint therapy in autoimmune diseases. Int Immunopharmacol. 2022; 107:108647. DOI: 10.1016/j.intimp.2022.108647. View

17.

Horisberger K, Portenkirchner C, Rickenbacher A, Biedermann L, Gubler C, Turina M . Long-term immune-related adverse events after discontinuation of immunotherapy. Immunotherapy. 2021; 13(9):735-740. DOI: 10.2217/imt-2020-0320. View

18.

Triebel F, JITSUKAWA S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E . LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med. 1990; 171(5):1393-405. PMC: 2187904. DOI: 10.1084/jem.171.5.1393. View

19.

Tian C, Ou Y, Chang S, Lin C . Pembrolizumab-induced myasthenia gravis-like disorder, ocular myositis, and hepatitis: a case report. J Med Case Rep. 2021; 15(1):244. PMC: 8086081. DOI: 10.1186/s13256-021-02722-8. View

20.

Borodic G, Hinkle D, Cia Y . Drug-induced graves disease from CTLA-4 receptor suppression. Ophthalmic Plast Reconstr Surg. 2011; 27(4):e87-8. DOI: 10.1097/IOP.0b013e3181ef72a1. View