{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:01:20Z","timestamp":1792612880566,"version":"4.5.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>TROP2 is a transmembrane glycoprotein implicated in tumor progression and immune regulation across epithelial malignancies and serves as a therapeutic target for antibody -drug conjugates. Its role in the tumor immune microenvironment of head and neck squamous cell carcinoma (HNSCC), particularly in the context of PD-1 blockade, remains insufficiently defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TROP2 protein expression was assessed by immunohistochemistry in 47 patients with HNSCC treated with anti -PD-1 therapy, including primary tumors and, in 27 cases, matched recurrent and\/or metastatic lesions. Expression was quantified using the immunoreactive score. Tumor-infiltrating immune cells (CD3, CD8, CD4, FOXP3, CCR4, and CD163) were analyzed in intra- and peritumoral compartments. In parallel, transcriptomic data from The Cancer Genome Atlas (TCGA; n = 483) were evaluated to explore associations between TROP2 mRNA expression and immune infiltration signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TROP2 expression was detected in 95% of tumors, with more than 80% showing moderate to high levels. Higher TROP2 expression was significantly associated with lower T status and showed a trend toward absence of distant metastasis but was not associated with nodal status, UICC stage, disease setting, or response to PD-1 blockade. Increased intratumoral CCR4+ and CD3+ T-cell infiltration correlated with improved survival. TCGA analysis demonstrated significant associations between TROP2 expression and multiple immune cell populations, including CD8+ and CD4+ T cells, Th2 cells, dendritic cells, macrophages, and TGF-\u03b2 -related signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings indicate that TROP2 is broadly expressed in HNSCC and linked to distinct immune microenvironment features, supporting its potential as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1901872","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:24:20Z","timestamp":1785990260000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["TROP2 expression in head and neck squamous cell carcinoma: association with the tumor immune microenvironment and clinical 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Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix L.","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ala-Addean","family":"Mustapha","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Wemmert","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University","place":["Homburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Schick","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University","place":["Homburg, 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