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Recent evidence suggests that human papillomavirus (HPV) is associated with ~35% of OAC. HPV-positive OAC patients have higher survivorship compared to HPV-negative patients, however current management remains uniform regardless of HPV status. Although the tumour microenvironment (TME), particularly intra-tumoural T-cell infiltration, is associated with improved outcomes in numerous cancers, characterisation of T-cell subsets in HPV-driven and HPV-independent OAC have not been explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Differences in T-cell subsets within OAC biopsies of HPV-positive (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200915) and HPV-negative (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922) were studied by multiplex immunofluorescence microscopy, in a retrospective cross-sectional study. Statistical analyses were conducted to assess differences in T-cell quantification, and to assess the correlation with patient prognosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Increased densities of FoxP3+ regulatory T-cells (Treg) and reduced CD8+:Treg ratios were evident in HPV-negative OAC compared to HPV-positive OAC. Other CD4+ and CD8+ subset densities were comparable. Univariate analyses demonstrated shorter overall survival (OS) in patients with high Treg proportions and low CD8+:Treg ratios. Multivariate analyses demonstrated a low total CD8+:Treg ratio to be independently associated with poor prognosis (HR 3.06; 95% CI 1.05\u201310.27;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.050), along with metastasis and absence of HPV infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We report novel evidence of an immunoregulatory TME in HPV-negative OAC, as indicated by high Treg proportions and low CD8+:Treg ratios. Future work may lead to improved risk stratification by the presence or absence of HPV, as well as utilising the CD8+:Treg ratio in the local TME as a predictive biomarker. Additionally, a more in-depth understanding of the TME would assist in the development of novel targeted immunotherapies, for example by modulating Tregs or CD8+ T-cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-025-07482-3","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T07:05:17Z","timestamp":1764227117000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HPV status shapes T-cell immunoprofiles in oesophageal adenocarcinoma: high regulatory T cell infiltration predicts poor prognosis"],"prefix":"10.1186","volume":"24","author":[{"given":"Subin","family":"Wui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0800-516X","authenticated-orcid":false,"given":"Rehana V.","family":"Hewavisenti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Rabiei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony D.","family":"Kelleher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahtab","family":"Farzin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanmugarajah","family":"Rajendra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5329-9072","authenticated-orcid":false,"given":"Sarah C.","family":"Sasson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"issue":"3","key":"7482_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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