{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:51:05Z","timestamp":1791179465783,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002923","name":"National Scientific and Technical Research Council","doi-asserted-by":"publisher","award":["PIP 112\u201020210100535CO"],"award-info":[{"award-number":["PIP 112\u201020210100535CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Thyroid cancer (TC) is the most common endocrine malignancy. While papillary thyroid cancer (PTC) generally has a favorable prognosis, anaplastic thyroid cancer (ATC) is rare but highly aggressive, with limited treatment options, highlighting the urgent need for novel therapeutic targets. Macrophages are a major component of the immune infiltrate in TC, and their abundance is associated with poor prognosis. We recently identified upregulation of the immune checkpoint TIM3 (T\u2010cell immunoglobulin and mucin\u2010domain containing protein 3) on M2\u2010like macrophages both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in ATC xenografts. In addition, we have shown that transforming growth factor \u03b21 (TGF\u03b21) promotes macrophage polarization toward an M2\u2010like phenotype. However, the role and clinical significance of TGF\u03b21 in regulating TIM3 expression in TC\u2010associated macrophages remains unclear. We found that TGF\u03b21 secreted by ATC cells significantly increased\n                    <jats:italic>HAVCR2<\/jats:italic>\n                    (TIM3) mRNA expression in human monocytes. Analysis of patient samples demonstrated elevated TIM3 expression in both PTC and ATC tissues compared with adenoma and normal thyroid counterparts. Analysis of publicly available single\u2010cell RNA sequencing datasets further showed increased TIM3 expression in T cells from both tumor types. Notably, TIM3 upregulation was also localized to M2\u2010like macrophages within the thyroid tumor microenvironment (TME), and positively correlated with\n                    <jats:italic>TGFB1<\/jats:italic>\n                    \/\n                    <jats:italic>CD163<\/jats:italic>\n                    expression, suggesting the involvement of a TGF\u03b2\u2013TIM3 axis in macrophages in TC. Combined targeting of the TIM3 and PD1 pathway in an immunocompetent mouse model of ATC led to a significant reduction in tumor growth. Together, these findings highlight TIM3 as a promising immunotherapeutic target in TC, with the potential to suppress macrophage\u2010mediated pro\u2010tumor activity while enhancing T\u2010cell\u2010driven anti\u2010tumor immunity within the thyroid TME. \u00a9 2026 The Pathological Society of Great Britain and Ireland. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.\n                  <\/jats:p>","DOI":"10.1002\/path.70104","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T05:35:06Z","timestamp":1785994506000},"page":"342-356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TIM3<\/scp>\n                    as a therapeutic target in anaplastic thyroid cancer: upregulation in\n                    <scp>M2<\/scp>\n                    \u2010like macrophages induced by tumor microenvironment\u2010derived\n                    <scp>TGF\u03b21<\/scp>"],"prefix":"10.1002","volume":"270","author":[{"given":"Agustina","family":"Jaroszewski","sequence":"first","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda. Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas. 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