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Although T-cell infiltration is common in follicular cell-derived thyroid cancers, tumor mutation burden is low. The antigenic potential of thyroid cancers is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the anti-tumor T-cell response in thyroid cancer, we expanded tumor-infiltrating lymphocytes (TIL) from primary thyroid tumors and tumor-involved lymph nodes (TILN). Putative neoantigens and both tissue-associated and tumor-associated antigens were identified by targeted sequencing and RNA-seq. HLA typing was performed for all patients, and neoantigen binding potential was predicted for each patient using NetMHCpan 4.1 and NetMHCIIpan 4.0 algorithms. In parallel, T-cell receptor \u03b2 sequencing was performed to detect T-cell clonal expansions in patient-matched primary tumors and TILN. TIL reactivity to tumor-associated antigens and neoantigens was determined in vitro by interferon \u03b3 ELISA and flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tumor-infiltrating T cells were evident in all thyroid tumors and readily expanded ex vivo. Shared clones were present in primary thyroid tumors and matched TILN in all patients tested, constituting 1% to 10% of the sequenced clones in 6\/8 patients. T-cell reactivity to thyroid tissue-specific proteins, thyroid peroxidase and thyroglobulin, was observed in 84.6% (11\/13) and 69.2% (9\/13) patients, respectively. A BrafV600E-specific T-cell response was evident in 80% (4\/5) BrafV600E+ patients. T cells reactive to gene fusion-derived neoantigens were detected in patients with TPR-NTRK1+ and CCDC6-RET+ thyroid cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our studies confirm the presence of tumor antigen-specific T cells in patients with thyroid cancer and encourage further exploration of T cell-targeted immunotherapies for patients with progressive, treatment refractory thyroid cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf639","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T13:13:25Z","timestamp":1763730805000},"page":"e1289-e1301","source":"Crossref","is-referenced-by-count":4,"title":["Tumor-infiltrating T Lymphocytes Recognize Thyroid-specific Proteins and Neo-antigens in Follicular Cell-derived Thyroid Cancers"],"prefix":"10.1210","volume":"111","author":[{"given":"Breaunna","family":"Garza","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]},{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5064-7958","authenticated-orcid":false,"given":"Jacob","family":"Calhoun","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]},{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-7703","authenticated-orcid":false,"given":"Paul J","family":"Norman","sequence":"additional","affiliation":[{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]},{"name":"Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Cline","sequence":"additional","affiliation":[{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]},{"name":"Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M","family":"Kichula","sequence":"additional","affiliation":[{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]},{"name":"Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3606-2428","authenticated-orcid":false,"given":"Ticiana D J","family":"Farias","sequence":"additional","affiliation":[{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]},{"name":"Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Sams","sequence":"additional","affiliation":[{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]},{"name":"Department of Pathology, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meher Preethi","family":"Boorgula","sequence":"additional","affiliation":[{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Danhorn","sequence":"additional","affiliation":[{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7005-8994","authenticated-orcid":false,"given":"Bryan R","family":"Haugen","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]},{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 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