{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:44:17Z","timestamp":1788813857581,"version":"build-2803163510"},"reference-count":47,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"27","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08CA191139"],"award-info":[{"award-number":["K08CA191139"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Conquer Cancer Young Investigator Award"},{"name":"American Society for Radiation Oncology Junior Faculty Award"},{"name":"Cedars-Sinai Precision Health Grant"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:p>\n                    Lymph node (LN) metastases are a major driver of mortality across solid cancers, including thyroid carcinomas, which are known for high rates of nodal colonization. To elucidate the determinants of nodal spread, we isolated tumor-infiltrating leukocytes from primary thyroid tumors and matched metastatic LNs for single-cell RNA sequencing with validation by multiplex immunohistochemistry. Comparing the microenvironmental alterations between primary tumors and their LNs, we found that thyrocytes and tumor-associated macrophages down-regulate the expression of multiple inflammatory cytokine receptors, including\n                    <jats:italic toggle=\"yes\">TNFRSF12A<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">CX3CR1<\/jats:italic>\n                    , upon LN colonization. LNs were associated with the induction of regulatory T cells to suppress T cell\u2013mediated cytotoxicity compared to matched primary tumors. Notably, tumor-infiltrating lymphocytes within LNs demonstrated increased expression of activation markers, including interleukin-7 receptor (\n                    <jats:italic toggle=\"yes\">IL7R<\/jats:italic>\n                    ). High LN expression of\n                    <jats:italic toggle=\"yes\">IL7R<\/jats:italic>\n                    was significantly correlated with improved outcomes and can serve as a biomarker in this heterogeneous disease. Our findings on the dynamic equilibrium within LN metastases may offer conserved mechanisms for nodal colonization across solid tumors.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea4727","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:58:28Z","timestamp":1783101508000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Single-cell transcriptomic analysis reveals tumor-immune determinants of lymph node colonization and progression in thyroid cancer"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-4623","authenticated-orcid":true,"given":"Anthony T.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA."},{"name":"Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA."},{"name":"Department of 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