Predictive and sensitive biomarkers for thyroid dysfunctions during treatment with immune‐checkpoint inhibitors
Open accessAbstract
Immune‐related adverse events (irAEs) are often seen during immune‐checkpoint inhibitor (ICI) treatment of various malignancies. Endocrine irAEs including thyroid dysfunctions are the most common irAEs, but their biomarkers remain unclear. In order to identify individuals who are susceptible to thyroid irAE for earlier diagnosis and appropriate follow‐up, the current study is aimed to investigate biomarkers of thyroid irAE. Herein, patients with advanced malignant diseases who received ICIs treatment were prospectively studied. Clinical and laboratory examination, thyroid function, and autoantibodies were evaluated at baseline, and every 4 wk after first treatment with ICIs. Cytokines/chemokines were measured at baseline and at 4 wk. In vivo effects of ICIs on experimental autoimmune thyroiditis were evaluated. Twenty‐six patients with malignant diseases who received ICIs treatment were enrolled in the study. Patients were divided into two groups: those who developed thyroid irAE, and those without irAEs. Comparing the two groups, early increase (≤4 wk) in serum thyroglobulin (Tg) levels and thyroid autoantibodies was seen in thyroid irAE (P < .05). Notably, higher levels of serum IL‐1β, IL‐2, and GM‐CSF at baseline, and early decrease of IL‐8, G‐CSF, and MCP‐1 were significantly associated in the development of thyroid irAE (P < .05). In vivo effects of anti‐PD‐1 antibody on deterioration of mice experimental thyroiditis were seen. In conclusion, early change in Tg, thyroid autoimmunity, and cytokine levels might indicate development of thyroid irAE. Pre‐existing thyroid autoimmunity might be involved with the development of thyroid irAE. Potential application of these factors as surrogate biomarkers for tumor therapy was indicated.
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Median time to presentation is 9-12 weeks for ipilimumab-treated patients and 26 weeks for anti-PD-1/PD-L1-treated patients.
“Median time to presentation is 9-12 weeks into treatment for ipilimumab-treated patients (monotherapy or combination) and 26 weeks into treatment for anti-PD-1/PD-L1.61”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [61]
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- [4]Inaba H, Ariyasu H, Okuhira H, et al. Endocrine dysfunctions during treatment of immune‐checkpoint inhibitors. Trends. Immunotherapy. 2018; 2: 1‐ 5. 10.24294/ti.v2i2.606 · DOI
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Endocrine toxicities of immune checkpoint inhibitors
Wright, J. J., Powers, A. C., & Johnson, D. B. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00484-3 · Cited by 441 · see citing works
- Authors
- Kurimoto, C., Inaba, H., Ariyasu, H., Iwakura, H., Ueda, Y., Uraki, S., Takeshima, K., Furukawa, Y., Morita, S., Yamamoto, Y., Yamashita, S., Katsuda, M., Hayata, A., Akamatsu, H., Jinnin, M., Hara, I., Yamaue, H., & Akamizu, T.
- Affiliations
- Wakayama Medical University (JP)
- The First Department of Medicine Wakayama Medical University Wakayama Japan
- Corresponding author
- Inaba, Hidefumi
- ORCID
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2020-03-17
- Volume
- 111
- Issue
- 5
- Pages
- 1468-1477
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC7226278
- OpenAlex
- W3008952136
- Cited by
- 160
- References
- 26
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 40 · 2023: 33 · 2022: 31 · 2021: 20 · 2020: 6
- FWCI
- 8.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Science (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Takeda Science Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- immune-related adverse events, immune checkpoint inhibitors, thyroid dysfunction, thyroid autoimmunity, thyroglobulin, thyroid autoantibodies, cytokines, biomarkers, experimental autoimmune thyroiditis, anti-PD-1, IL-1β, interleukin-2, GM-CSF, advanced cancer
- MeSH terms
- Aged, Aged, 80 and over, Animals, Autoantibodies, Disease Models, Animal, Female, Humans, Immunologic Factors, Immunotherapy, Male, Middle Aged, Neoplasms, Prospective Studies, Thyroglobulin, Thyroid Diseases, Thyroid Gland, Thyroiditis, Autoimmune, Biomarkers, Cytokines, Mice, Programmed Cell Death 1 Receptor
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