ArticleThyroid : official journal of the American Thyroid Association2016
Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase.
Article in Thyroid : official journal of the American Thyroid Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- Predicting immune-related thyroiditis using polygenic risk scores in patients with advanced melanoma.Journal for immunotherapy of cancer · 2026Article
- Clonally expanded, thyrotoxic effector CD8Science translational medicine · 2023Article
- Current understanding of CTLA-4: from mechanism to autoimmune diseases.Frontiers in immunology · 2023Review
- Inhibition of IL-17A Protects against Thyroid Immune-Related Adverse Events while Preserving Checkpoint Inhibitor Antitumor Efficacy.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Distinct Cytokine Signatures in Thyroiditis Induced by PD-1 or CTLA-4 Blockade: Insights from a New Mouse Model.Thyroid : official journal of the American Thyroid Association · 2021Article
- Insights into immune checkpoint inhibitor-induced thyroiditis.Nature reviews. Endocrinology · 2021Article
- Hypothalamic-Pituitary Autoimmunity in Patients Treated with Anti-PD-1 and Anti-PD-L1 Antibodies.Cancers · 2021Article
- Yanghe Decoction Suppresses the Experimental Autoimmune Thyroiditis in Rats by Improving NLRP3 Inflammasome and Immune Dysregulation.Frontiers in pharmacology · 2021Article
- The Efficacy and Safety of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease.Frontiers in oncology · 2021Review
- Peri-tumor administration of controlled release anti-CTLA-4 synergizes with systemic anti-PD-1 to induce systemic antitumor immunity while sparing autoimmune toxicity.Cancer immunology, immunotherapy : CII · 2020Article
- To reflect human autoimmune thyroiditis, thyroid peroxidase (not thyroglobulin) antibodies should be measured in female (not sex-independent) NOD.H2Clinical and experimental immunology · 2019Article
- Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints.Endocrine reviews · 2019Review
- Immunomodulatory Factors Galectin-9 and Interferon-Gamma Synergize to Induce Expression of Rate-Limiting Enzymes of theFrontiers in immunology · 2016Article
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3 authors at 1 institution in 1 country.
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Abstract
backgroundCytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2(h4) mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water.
methodsNOD-H2(h4) mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls.
resultsCTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory environment.
conclusionsThis study shows that CTLA-4 blockade exacerbates the iodine-accelerated form of thyroiditis typical of the NOD-H2(h4) mouse. The study could also have implications for cancer patients who develop thyroiditis as an immune-related adverse event after CTLA-4 blockade.
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