Immune checkpoint inhibitor therapies induce potent anti-tumour immunity as well as immune-related adverse events that manifest as autoimmune disease — particularly thyroiditis. Translational studies and preclinical models are beginning to unravel the molecular processes that mediate these adverse events; this knowledge might enable the development of ICIs with anti-tumour efficacy and improved safety margins.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Shankar, B. et al. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer. JAMA Oncol. 6, 1952–1956 (2020).
Muir, C. A. et al. Thyroid immune-related adverse events following immune checkpoint inhibitor treatment. J. Clin. Endocrinol. Metab. https://doi.org/10.1210/clinem/dgab263 (2021).
Yasuda, Y. et al. CD4+ T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice. Sci. Trans. Med. 13, eabb7495 (2021).
Fan, Y. et al. Association of immune related adverse events with efficacy of immune checkpoint inhibitors and overall survival in cancers: a systemic review and meta-analysis. Front. Oncol. 11, 633032 (2021).
Liu, J. et al. Assessing immune-related adverse events of efficacious combination immunotherapies in preclinical models of cancer. Cancer Res. 76, 5288–5301 (2016).
Perez-Ruiz, E. et al. Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy. Nature 569, 428–432 (2019).
Sharma, R., Di Dalmazi, G. & Caturegli, P. Exacerbation of autoimmune thyroiditis by CTLA-4 blockade: a role for IFNγ-induced indoleamine 2, 3-dioxygenase. Thyroid 26, 1117–1124 (2016).
Álvarez-Sierra, D. et al. Analysis of the PD-1/PD-L1 axis in human autoimmune thyroid disease: insights into pathogenesis and clues to immunotherapy associated thyroid autoimmunity. J. Autoimmun. 103, 102285 (2019).
Kotwal, A. et al. Immune checkpoint inhibitor-induced thyroiditis is associated with increased intrathyroidal T lymphocyte subpopulations. Thyroid 30, 1440–1450 (2020).
Horie, I. et al. Induction of autoimmune thyroiditis by depletion of CD4+CD25+ regulatory T cells in thyroiditis-resistant IL-17, but not interferon-γ receptor, knockout nonobese diabetic-H2 h4 mice. Endocrinology 152, 4448–4454 (2011).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Lechner, M.G., Ryder, M. Insights into immune checkpoint inhibitor-induced thyroiditis. Nat Rev Endocrinol 17, 643–644 (2021). https://doi.org/10.1038/s41574-021-00557-3
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41574-021-00557-3
