{"doi":"10.1089/thy.2020.0075","title":"Immune Checkpoint Inhibitor-Induced Thyroiditis Is Associated with Increased Intrathyroidal T Lymphocyte Subpopulations","abstract":"Background: Immune checkpoint inhibitors (ICIs) frequently cause thyroid dysfunction but their underlying mechanism remains unclear. We have previously demonstrated increased circulating natural killer (NK) cells and human leukocyte antigen (HLA)-DR surface expression on inflammatory intermediate CD14 + CD16 + monocytes in programmed cell death protein-1 (PD-1) inhibitor-treated patients. This study characterizes intrathyroidal and circulating immune cells and class II HLA in ICI-induced thyroiditis. Methods: This is a single-center prospective cohort study of 10 patients with ICI-induced thyroiditis by flow cytometry of thyroid fine needle aspirates ( n = 9) and peripheral blood ( n = 7) as compared with healthy thyroid samples ( n = 5) and healthy volunteer blood samples ( n = 44); HLA class II was tested in n = 9. Results: ICI-induced thyroiditis samples demonstrated overall increased T lymphocytes (61.3% vs. 20.1%, p = 0.00006), CD4 − CD8 − T lymphocytes (1.9% vs. 0.7%, p = 0.006), and, as a percent of T lymphocytes, increased CD8 + T lymphocytes (38.6% vs. 25.7%; p = 0.0259) as compared with healthy thyroid samples. PD-1 inhibitor-induced thyroiditis had increased CD4 + PD1 + T lymphocytes (40.4% vs. 0.8%; p = 0.021) and CD8 + PD1 + T lymphocytes (28.8% vs. 1.5%; p = 0.038) in the thyroid compared with the blood. Circulating NK cells, certain T lymphocytes (CD4 + CD8 + , CD4 − CD8 − T, gamma – delta), and intermediate monocytes were increased in ICI-induced thyroiditis. Six patients typed as HLA-DR4-DR53 and three as HLA-DR15. Conclusions: ICI-induced thyroiditis is a T lymphocyte-mediated process with intra-thyroidal predominance of CD8 + and CD4 − CD8 − T lymphocytes. The HLA haplotypes may be involved but need further evaluation. These findings expand the limited understanding of ICI-induced thyroiditis, which could be further translated to guide immunomodulatory therapies for advanced thyroid cancer.","journal":"Thyroid","year":2020,"id":54737,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":100,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9666,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":281797,"name":"Michael P. Gustafson","orcid":"0000-0002-5514-7072","position":1,"is_corresponding":false},{"id":283559,"name":"Svetlana Bornschlegl","orcid":null,"position":2,"is_corresponding":false},{"id":281798,"name":"Lisa A. Kottschade","orcid":"0000-0001-8922-2619","position":3,"is_corresponding":false},{"id":239606,"name":"Danae A. Delivanis","orcid":"0000-0003-4868-0423","position":4,"is_corresponding":false},{"id":281799,"name":"Allan B. Dietz","orcid":"0000-0003-3410-9621","position":5,"is_corresponding":false},{"id":281800,"name":"Manish J. Gandhi","orcid":"0000-0001-7210-1909","position":6,"is_corresponding":false},{"id":281801,"name":"Mabel Ryder","orcid":"0000-0002-0520-6505","position":7,"is_corresponding":false},{"id":281796,"name":"Anupam Kotwal","orcid":"0000-0002-4500-8546","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T21:04:14.743014Z","pmid":"32323619","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}