ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 3.5 | DOI: 10.1530/ey.18.3.5

ESPEYB18 3. Thyroid Drug induced thyroid disease (1 abstracts)

3.5. Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade

Khan Z , Hammer C , Carroll J , Di Nucci F , Acosta SL , Maiya V , Bhangale T , Hunkapiller J , Mellman I , Albert ML , McCarthy MI & Chandler GS



Nat Commun. 2021 Jun 7;12(1):3355. doi: 10.1038/s41467-021-23661-4.

This study describes the interaction of individual genetic variation for autoimmune thyroid disease with risk of thyroid immune related adverse events (irAE) during or after immune checkpoint inhibitor (ICI) treatment for advanced cancer.

ICIs are monoclonal antibodies blocking T-cell exhaustion and resulting in a T-cell antitumor response. However, ICIs are associated with irAE. Reversible destructive thyroiditis, hyperthyroidism and hypothyroidism (thyroid irAE) are the most frequent endocrine side effects of anti-programmed cell death-1 antibodies (PD-1-AB), one frequently used ICI. Further endocrine irAE are type 1 diabetes, adrenal insufficiency and hypophysitis [1]. Anti-thyroid antibodies before treatment seem critical for development of PD-1-AB induced thyroid irAE mediated by cytotoxic CD4(+) T cells [2,3].

In this large analysis of data from 7 PD-1 blockade trials, the authors found that hypothyroidism was more frequent than hyperthyroidism in the context of thyroid irAE, and was associated with longer survival of the treated cancer patients. To investigate the role of genetic variation for thyroid irAE, the authors developed a polygenic risk score for hypothyroidism using GWAS. They observed that patients with high lifetime genetic susceptibility for autoimmune thyroid disease (indicated by high polygenic risk score) also had higher risk for PD-1 blockade induced thyroid irAE.

This study extends current evidence that not only manifest biochemical or radiological signs of Hashimoto thyroiditis [1,3] but even genetic susceptibility for autoimmune thyroid disease/hypothyroidism predicts risk for thyroid irAE. Both, genetic and clinical information allow personalized decision making in cancer patients.

Reference: 1. Muir CA, Clifton-Bligh RJ, Long GV, Scolyer RA, Lo SN, Carlino MS, Tsang VHM, Menzies AM. Thyroid immune-related adverse events following immune checkpoint inhibitor treatment. J Clin Endocrinol Metab. 2021 Apr 20:dgab263. doi: 10.1210/clinem/dgab263. 2. Yasuda Y, Iwama S, Sugiyama D, Okuji T, Kobayashi T, Ito M, Okada N, Enomoto A, Ito S, Yan Y, Sugiyama M, Onoue T, Tsunekawa T, Ito Y, Takagi H, Hagiwara D, Goto M, Suga H, Banno R, Takahashi M, Nishikawa H, Arima H. CD4(+) T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in thyroglobulin-immunized mice. Sci Transl Med. 2021;13(593):eabb7495. doi: 10.1126/scitranslmed.abb7495.3. Okada N, Iwama S, Okuji T, Kobayashi T, Yasuda Y, Wada E, Onoue T, Goto M, Sugiyama M, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Hase T, Morise M, Kanda M, Yokota K, Hashimoto N, Ando M, Fujimoto Y, Nagino M, Kodera Y, Fujishiro M, Hibi H, Sone M, Kiyoi H, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Arima H. Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study. Br J Cancer. 2020 Mar;122(6):771–777. doi: 10.1038/s41416-020-0736-7.

Article tools

My recent searches

No recent searches.