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Using a 4-nitroquinoline-1-oxide (4NQO)-induced oral carcinogenesis mouse model, we evaluated GA\u2019s effects on tumor progression, immune modulation, and stress-hormone-related pathways. Phenotypic outcomes were assessed by histopathology, proliferation markers, and in vitro cytotoxicity assays. Transcriptomic changes were profiled by RNA sequencing, pathway enrichment and validation using RT-qPCR, Western blotting, ELISA, and flow cytometry. GA selectively inhibited proliferation of HNSCC cell lines (CAL27, SCC83) while sparing normal oral epithelial cells (TE1177). In vivo, GA reduced tumor burden and histopathologic severity without affecting body weight. RNA-seq analysis revealed coordinated modulation of immune and stress-response pathways, including upregulation of\n                    <jats:italic>Carmil2<\/jats:italic>\n                    ,\n                    <jats:italic>Cd27<\/jats:italic>\n                    , and\n                    <jats:italic>Cd209d<\/jats:italic>\n                    and downregulation of\n                    <jats:italic>Fos<\/jats:italic>\n                    ,\n                    <jats:italic>Pappa<\/jats:italic>\n                    , and\n                    <jats:italic>Hif1a<\/jats:italic>\n                    . GA increased HSD11\u03b22 expression in vitro and in vivo and reduced cortisol in cAMP-stimulated HNSCC cells, findings consistent with reduced local glucocorticoid signaling. GA also increased IL-2 and decreased IL-10 in T cells, reduced monocytic MDSCs, and lowered PD-L1 on pro-inflammatory macrophages. Together, these findings identify HSD11\u03b22\/glucocorticoid metabolism as a potential axis associated with GA-mediated oral cancer chemoprevention.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-50700-1","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T03:56:31Z","timestamp":1777262191000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gallic acid chemoprevention of oral carcinogenesis is associated with HSD11\u03b22 upregulation and immune remodeling"],"prefix":"10.1038","volume":"16","author":[{"given":"Puja","family":"Upadhaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe F.","family":"Lamenza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Ramalingam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishan Kumar","family":"Nyati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmitha","family":"Jagadeesha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvekshya","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reegan","family":"Kehres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Kazmierowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali","family":"Dasari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaheer","family":"Masood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyton","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Pracha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Oghumu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"50700_CR1","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.semcancer.2020.06.014","volume":"80","author":"E Khatoon","year":"2022","unstructured":"Khatoon, E. et al. 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