{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:43:30Z","timestamp":1792190610130,"version":"4.4.0"},"reference-count":41,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context:<\/jats:title><jats:p>Papillary thyroid cancer (PTC) is characterized by a lymphocytic infiltration. PTC patients with lymphocytic infiltration may have a better clinical outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective:<\/jats:title><jats:p>Characterization of tumor epitope-specific immunity and correlation analyses with the clinical outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients:<\/jats:title><jats:p>150 PTC patients; 40 Hashimoto thyroiditis (HT) patients; 21 healthy controls; 27,239 healthy whites (for HLA typing).<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures:<\/jats:title><jats:p>HLA class I restricted thyroperoxidase (TPO) and thyroglobulin (Tg) epitope-specific T cells (tetramer analyses), correlation analyses between HLA class II phenotypes, T cell immunity, and the clinical course.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>The frequency of TPO- and Tg-specific CD8+ T cells in PTC patients was largely increased compared with healthy controls (TPO and Tg, P &amp;lt; 0.005 and P &amp;lt; 0.005) and was similar to those in HT patients. HLA-DQB1*03\u2013positive PTC patients had a significantly lower risk [risk ratio (RR), 0.170; 95% confidence interval (CI), 0.037 to 0.755; P &amp;lt; 0.05] and HLA-DRB1*03\u2013positive and HLA-DQB1*02\u2013positive PTC patients a significantly higher risk (HLA-DRB1*03: RR, 4.400; 95% CI, 1.378 to 14.05; P &amp;lt; 0.05; HLA-DQB1*02: RR, 3.692; 95% CI, 1.102 to 12.38; P &amp;lt; 0.05) for distant metastases, compared with patients with other haplotypes. HLA-DQB1*03\u2013positive PTC patients revealed an increased responsiveness of tumor epitopes in vitro. These tumor epitope-specific CD8+ T cells were also found in lymph node metastases of HLA-DQB1*03\u2013positive PTC patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p>We demonstrate a tumor epitope-specific immunity in PTC patients and the protective role of HLA-DQB1*03 against metastatic spread. These results have direct implications for new treatment options with immune checkpoint inhibitors.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2016-2469","type":"journal-article","created":{"date-parts":[[2016,11,18]],"date-time":"2016-11-18T19:03:29Z","timestamp":1479495809000},"page":"2154-2161","source":"Crossref","is-referenced-by-count":14,"title":["Epitope-Specific Antitumor Immunity Suppresses Tumor Spread in Papillary Thyroid Cancer"],"prefix":"10.1210","volume":"102","author":[{"given":"Margret","family":"Ehlers","sequence":"first","affiliation":[{"name":"Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kuebart","sequence":"additional","affiliation":[{"name":"Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubertus","family":"Hautzel","sequence":"additional","affiliation":[{"name":"Clinic for Nuclear Medicine, University Hospital Duesseldorf, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Enczmann","sequence":"additional","affiliation":[{"name":"Institute for Transplantation Diagnostics and Cell Therapeutics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Carinna","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Medical School, Heinrich Heine University, 40225 Duesseldorf, Germany"},{"name":"Institute of Pathology, University Hospital of Essen, University of Duisburg\u2013Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Haase","sequence":"additional","affiliation":[{"name":"Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Allelein","sequence":"additional","affiliation":[{"name":"Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Dringenberg","sequence":"additional","affiliation":[{"name":"Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Schmid","sequence":"additional","affiliation":[{"name":"Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schott","sequence":"additional","affiliation":[{"name":"Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2016,11,18]]},"reference":[{"issue":"9","key":"2020071620500290600_B1","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1002\/ijc.29251","article-title":"Thyroid cancer mortality and incidence: a global overview","volume":"136","author":"La Vecchia","year":"2015","journal-title":"Int J Cancer"},{"issue":"10","key":"2020071620500290600_B2","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1055\/s-0035-1548832","article-title":"The pathogenesis of Hashimoto\u2019s thyroiditis: further developments in our understanding","author":"Ajjan","year":"2015","journal-title":"Horm Metab Res"},{"key":"2020071620500290600_B3","doi-asserted-by":"crossref","unstructured":"Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R. 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