{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:19:55Z","timestamp":1783664395198,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Israel Endocrine Society","award":["3-15112"],"award-info":[{"award-number":["3-15112"]}]},{"name":"The Israel Ministry of Health","award":["3-15112"],"award-info":[{"award-number":["3-15112"]}]},{"name":"Sasson and Luisa Naor Fund","award":["3-15112"],"award-info":[{"award-number":["3-15112"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Immune checkpoint inhibitors (ICI) are commonly associated with thyroid immune-related adverse events, yet the mechanism has not been fully elucidated. We aimed to further explore the mechanism of ICI-induced thyroid dysfunction by assessing changes induced in the thyroid transcriptome by ICI treatment (\u03b1PD-1\/\u03b1PD-L1) in a lung cancer murine model. RNA-sequencing of thyroid tissues revealed 952 differentially expressed genes (DEGs) with \u03b1PD-1 treatment (|fold-change| \u22651.8, FDR &lt; 0.05). Only 35 DEG were identified with \u03b1PD-L1, and we therefore focused on the \u03b1PD-1 group alone. Ingenuity Pathway Analysis revealed that of 952 DEGs with \u03b1PD-1 treatment, 362 were associated with functions of cell death and survival, with predicated activation of pathways for apoptosis and necrosis (Z = 2.89 and Z = 3.21, respectively) and negative activation of pathways for cell viability and cell survival (Z = \u22126.22 and Z = \u22126.45, respectively). Compared to previously published datasets of interleukin-1\u03b2 and interferon \u03b3-treated human thyroid cells, apoptosis pathways were similarly activated. However, unique changes related to organ inflammation and upstream regulation by cytokines were observed. Our data suggest that there are unique changes in gene expression in the thyroid associated with \u03b1PD-1 therapy. ICI-induced thyroid dysfunction may be mediated by increased tissue apoptosis resulting in destructive thyroiditis.<\/jats:p>","DOI":"10.3390\/ijms241310526","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T01:42:32Z","timestamp":1687743752000},"page":"10526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RNA Sequencing Reveals Unique Transcriptomic Signatures of the Thyroid in a Murine Lung Cancer Model Treated with PD-1 and PD-L1 Antibodies"],"prefix":"10.3390","volume":"24","author":[{"given":"Rena","family":"Pollack","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Stokar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natan","family":"Lishinsky","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Gurt","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Kaisar-Iluz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Institute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merav E.","family":"Shaul","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Institute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi G.","family":"Fridlender","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Institute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka","family":"Dresner-Pollak","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1158\/1078-0432.CCR-14-1860","article-title":"Immune escape mechanisms as a guide for cancer immunotherapy","volume":"21","author":"Beatty","year":"2015","journal-title":"Clin. 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