{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:05:12Z","timestamp":1784613912255,"version":"3.55.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Advances in single-cell technologies have provided detailed insight into cellular heterogeneity within tumor microenvironments. However, the regulatory mechanisms driving macrophage-mediated immune suppression in thyroid cancer remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied integrated single-cell multi-omics approaches to tumor samples from patients and murine thyroid cancer models, including single-cell RNA sequencing, single-cell ATAC sequencing, mass cytometry, spatial\/histological validation, and in vitro and in vivo functional assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a prominent enrichment of TREM2\n                      <jats:sup>+<\/jats:sup>\n                      tumor-associated macrophages within the thyroid cancer immune microenvironment. These macrophages displayed an immunosuppressive transcriptional and metabolic profile and promoted immune evasion through activation of the AHR\u2013IDO1\u2013kynurenine signaling axis, leading to impaired CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell function. Pharmacological inhibition of AHR and IDO1 reversed immune suppression and reduced tumor burden in experimental models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings reveal a TREM2\n                      <jats:sup>+<\/jats:sup>\n                      macrophage-driven immunometabolic mechanism in thyroid cancer and suggest that targeting the AHR\u2013IDO1\u2013kynurenine pathway may provide a potential strategy for improving antitumor immunity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1826288","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:35:49Z","timestamp":1784612149000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the AHR\u2013IDO1\u2013kynurenine pathway in TREM2+ macrophages restores antitumor immunity in thyroid cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Fei","family":"Le","sequence":"first","affiliation":[{"name":"Department of Head and Neck Tumor Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianming","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Pathology, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youfang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Tumor Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiping","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyao","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical College of Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00035-3","article-title":"The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020","volume":"10","author":"Pizzato","year":"2022","journal-title":"Lancet Diabetes 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