ArticleJournal of translational medicine2025
HPV status shapes T-cell immunoprofiles in oesophageal adenocarcinoma: high regulatory T cell infiltration predicts poor prognosis.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOesophageal adenocarcinoma (OAC) outcomes remain poor, with a 5-year survival rate of ~20%. 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.
methodsDifferences in T-cell subsets within OAC biopsies of HPV-positive (n = 15) and HPV-negative (n = 22) 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.
resultsIncreased 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 1.05-10.27; p = 0.050), along with metastasis and absence of HPV infection.
conclusionWe 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.
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